Synthesis and structure-activity relationships of novel benzoxaboroles as a new class of antimalarial agents

A series of boron-containing benzoxaborole compounds was designed and synthesized for a structure-activity relationship investigation surrounding 7-(HOOCCH₂CH₂)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (1) with the goal of discovering a new antimalarial treatment. Compound 1 demonstrates the best potency (IC₅₀ = 26 nM) against Plasmodium falciparum and has good drug-like properties, with low molecular weight (206.00), low ClogP (0.86) and high water solubility (750 μg/mL at pH 7).     

Twenty‐Four‐Hour and Annual Variation in Onset of Epistaxis in Osler Disease

Osler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi‐systemic haemorrhages. Recurrent epistaxis is the predominant symptom in more than 90% of patients. Recent studies showed circadian and seasonal patterns in the onset of nosebleeds, similar to acute cardiovascular events, such as myocardial infarction and stroke. The aim of this study was to determine whether such patterns would also apply to the onset of epistaxis in patients with Osler disease. In all, 110 patients with Osler disease who were under treatment for recurrent epistaxis at the University Hospital of Mannheim were requested to complete a questionnaire addressing the intensity and frequency of epistaxis according to the classification of Bergler et al., as well as circadian and circannual rhythmicity in the occurrence of epistaxis according to visual analogue scales (VAS). More than half of the patients claimed to experience daily to weekly episodes of recurrent epistaxis. The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak in the morning (05∶00–8∶00 h) and smaller secondary peaks in the evening (17∶00–20∶00 h and 21∶00–00∶00 h). No significant seasonal variation was found in the onset of epistaxis. However, a slight tendency, with a peak in winter months, was observed. Similar to other chronobiological studies on nosebleeds, this study showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even applied to patients with Osler disease. Further investigations are necessary to determine the pathological mechanism underlying this phenomenon.     

Twenty-four-hour and annual variation in onset of epistaxis in Osler disease

Osler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi-systemic haemorrhages. Recurrent epistaxis is the predominant symptom in more than 90% of patients. Recent studies showed circadian and seasonal patterns in the onset of nosebleeds, similar to acute cardiovascular events, such as myocardial infarction and stroke. The aim of this study was to determine whether such patterns would also apply to the onset of epistaxis in patients with Osler disease. In all, 110 patients with Osler disease who were under treatment for recurrent epistaxis at the University Hospital of Mannheim were requested to complete a questionnaire addressing the intensity and frequency of epistaxis according to the classification of Bergler et al., as well as circadian and circannual rhythmicity in the occurrence of epistaxis according to visual analogue scales (VAS). More than half of the patients claimed to experience daily to weekly episodes of recurrent epistaxis. The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak in the morning (05:00-8:00 h) and smaller secondary peaks in the evening (17:00-20:00 h and 21:00-00:00 h). No significant seasonal variation was found in the onset of epistaxis. However, a slight tendency, with a peak in winter months, was observed. Similar to other chronobiological studies on nosebleeds, this study showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even applied to patients with Osler disease. Further investigations are necessary to determine the pathological mechanism underlying this phenomenon.     

Minimum information about a marker gene sequence (MIMARKS) and minimum information about any (x) sequence (MIxS) specifications

Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences--the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The 'environmental packages' apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.     

A melanin-dispersing effect of cyclic adenosine monophosphate on Fundulus melanophores

Treatment of Fundulus melanophores with adenosine 3′,5′-monophosphate (cyclic AMP) is followed by reversible melanin dispersion in these cells. Adenosine 3′-monophosphate and adenosine 5′-monophosphate both have a similar, but weaker dispersing action. In addition, adenosine 5′-monophosphate also has a melanin aggregating effect. These results are interpreted to mean that nerve transmitters may act by controlling the level of cyclic AMP within the Fundulus melanophore.     

Adjuvant radiotherapy in malignant tumors of parotid. Experience of the Navarra Hospital Complex

BackgroundThe objective of the study was to review the outcome of patients with parotid cancer treated with postoperative radiotherapy at Complejo Hospitalario de Navarra in the last ten years.Materials and methodsWe retrospectively reviewed patients treated with adjuvant radiotherapy between January 2008 and December 2018. We analyzed demographic data, histopathologic findings, local control (LC) and overall survival (OS).ResultsA total of 40 patients received postoperative radiotherapy during the period mentioned. There were 22 men (55%) and 18 women (45%). Median age was 58 years (19–90). By tumor histology, the most common was squamous cell carcinoma (22.5%) followed by ex-pleomorphic adenoma (15%) and adenoid cystic carcinoma (10%). According to Surgery, 19 patients (47.5%) underwent a total parotidectomy, 20 (50%) partial parotidectomy, and 1 (2.5%) a radical parotidectomy. Twenty-one patients (51.2%) underwent cervical dissection, most of them being supraomohyoid (31.7%). Reasons for adjuvant RT were: R1 resection (35% of the patients), high grade tumors (27.5%) and 17.5% because R1 surgery and R1. Radiation was administered using IMRT in most patients to a total dose of 60 Gy in 30 fractions. The 5-year overall survival (OS) (Kaplan-Meier) was 81% (95% CI: 68.5–96.2%), and 10-years — 64%. The 5-year local control (LC) (Kaplan-Meier) was 82.4% (95% CI: 91.46–73.33%) and the 10-year LC — 72.2% (95% CI: 54.9–96%). To date, only 4 patients (10%) have died due to their parotid tumor.ConclusionThe adjuvant radiotherapy added to surgery, significantly reduces the risk of recurrence in high-risk patients with a very acceptable survival rate.     

Mortality of Sockeye Salmon Raised Under Light Backgrounds of Different Spectral Composition

Salmon from a 3 male×3 female sockeye salmon cross were raised under three different light regimes (UV: 300–850nm for 8 hoursday^-1, visible: 400–850nm for 8 hoursday^-1, and a control in which eggs were kept in darkness until hatching, followed by increasing amounts of light as the embryos approached swim-up) up to the parr interval (105 days from fertilization). The dose rates (Wm^-2), and total intensities per day (Jm^-2), for each treatment were less than 0.46 and 0.28 times of those measured in the shaded part of a stream, respectively. Egg mortality was higher for the UV and visible treatments compared to the control, and the number of alevins alive after day 83 was significantly different between treatments: highest for the control and lowest for the UV treatment. Eggs and hatched fish from female F2 suffered higher mortality than those from the other two females raising the possibility that sensitivity to UV-B in sockeye salmon may be either a maternally inherited trait or due to physiological or physical differences between egg groups. Alevins and parr from the control treatment transferred to the UV treatment suffered little mortality compared to animals raised in the UV and visible treatments from fertilization. These results, in conjunction with light measurements from streams, suggest that light and UV-B radiation could be a source of young salmon mortality in perturbed environments such as those resulting after forestry intervention.