In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.     

Dental esthetics and quality of life in adults with severe malocclusion before and after treatment

Objective:To investigate the association between satisfaction with dental esthetics and quality of life, and esthetics satisfaction in relation to esthetic evaluations of three panel groups.Materials and Methods:Fifty-two patients (36 women, 16 men; age 18–61 years) with severe malocclusion were treated in Oulu University Hospital. Of these, 38 and 14 patients underwent orthodontic/surgical treatment and orthodontic treatment, respectively. A questionnaire and dental photographs were collected before and after treatment. The 14-item Oral Health Impact Profile (OHIP-14) was used to measure oral health-related quality of life. Satisfaction with dental esthetics was evaluated using the Visual Analogue Scale. Dental photographs were presented to three panel groups: 30 laypersons, 30 dental students, and 10 orthodontists, who rated the photographs using the Aesthetic Component of the Index of Orthodontic Treatment Need.Results:Oral health–related quality of life (OHIP-14 severity score) and esthetic satisfaction (according to the Visual Analogue Scale) improved after the treatment (P < .001). The most unsatisfied patients reported oral effects more often both before and after treatment. Changes in oral health–related quality of life components of severity, psychological discomfort, and psychological disability correlated positively with the changes in esthetic satisfaction. Orthodontists graded the situation before treatment as worse and the outcome as better than the laypersons; the level of grading by dental students fell between these two groups.Conclusion:Improvement in esthetic satisfaction due to the treatment of severe malocclusion improves oral health–related quality of life, particularly by decreasing psychological discomfort and psychological disability.     

Pressure injury prevalence and incidence in acute inpatient care and related risk factors: A cross‐sectional national study

The aim of this national cross‐sectional study was to explore the prevalence of pressure injuries and incidence of hospital‐acquired pressure injuries, and the relating factors in somatic‐specialised inpatient care in Finland. The study was conducted in 16 (out of 21) Finnish health care organisations offering specialised health care services. Data were collected in 2018 and 2019 from adult patients (N = 5902) in inpatient, emergency follow‐up, and rehabilitation units. Pressure injury prevalence (all stages/categories) was 12.7%, and the incidence of hospital‐acquired pressure injuries was 10%. Of the participants, 2.6% had at least one pressure injury at admission. The risk of hospital‐acquired pressure injuries was increased for medical patients with a higher age, the inability to move independently, mode of arrival, being underweight, and the absence of a skin assessment or pressure injury risk assessment at admission. For surgical patients, the risk was associated with the inability to move independently, mode of arrival, and lack of skin assessment at admission, while being overweight protected the patients. Overall, medical patients were in greater risk of hospital‐acquired pressure injuries than the surgical patients. An assessment of the pressure injury risk and skin status should be carried out more systematically in Finnish acute care hospitals.     

N2 event-related potential correlates of response inhibition in an auditory Go/Nogo task.

The aim of this study was to investigate the event-related potential correlates of response inhibition in the N2 time window, specifically in the auditory modality. A paired tone Go/Nogo paradigm elicited an enhanced fronto-central negativity in the Nogo condition, which was accompanied by a concurring inferior fronto-temporal positivity. In contrast to most previous studies our data provide evidence for a fronto-central Nogo-N2 component in the auditory modality.     

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.     

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person‐years of exposure to warfarin‐only and 60,253 years of exposure to warfarin‐with‐statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin‐with‐statin compared to warfarin‐only and to allow multiple episodes per patient and time‐dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable‐adjusted RR = 0.98, 95% CI 0.89–1.07) or to simvastatin (RR = 1.01, 95% CI 0.91–1.11) with warfarin compared to exposure to warfarin‐only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.     

Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipoluscinosis

Zhong N, Wisniewski KE, Hartikainen J, Ju W, Moroziewicz DN, McLendon L, Sklower Brooks S, Brown WT. Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis
Late infantile neuronal ceroid lipofuscinosis (LINCL) is one of the most common pediatric neuronal degenerative disorders. A candidate gene underlying this disease, designated CLN2, was recently cloned and the gene product was characterized as a lysosomal pepstatin-insensitive carboxypeptidase (LPIC). Four mutations were identified in CLN2 from three unrelated LINCL individuals. To investigate further the mutation frequency in LINCL, we screened 16 LINCL probands for these four mutations. The previously reported intronic mutation, T523–1 G°C, was found in 56% (9/16) of the cases, of which two were homozygous and accounted for 34% (11/32) of LINCL chromosomes. The previously reported nonsense mutation, 636 C→T leading to R208stop, was found in 31% (5/16) of the cases, including one ho-mozygote and accounted for 19% (6/32) of LINCL chromosomes. Two previously described missense mutations, 1107 T°C and 1108 G→A, were not detected in any of these 16 probands. In total, the two observed mutations, T523–1 G°C and 636 C→T, accounted for 53% (17/32) of LINCL alleles. Thus, one or both mutations were seen in 11 (69%) cases and no mutation has yet been identified in five. Our finding that these two mutations are common in LINCL cases adds further evidence in support of the idea that dysfunction of LPIC underlies LINCL. Positive molecular testing can now complement clinical diagnosis of LPIC and will allow for pre-natal diagnosis for subsequent pregnancies.     

Human ROBO1 regulates interaural interaction in auditory pathways

In rodents, the Robo1 gene regulates midline crossing of major nerve tracts, a fundamental property of the mammalian CNS. However, the neurodevelopmental function of the human ROBO1 gene remains unknown, apart from a suggested role in dyslexia. We therefore studied axonal crossing with a functional approach, based on magnetoencephalography, in 10 dyslexic individuals who all share the same rare, weakly expressing haplotype of the ROBO1 gene. Auditory-cortex responses were recorded separately to left- and right-ear sounds that were amplitude modulated at different frequencies. We found impaired interaural interaction that depended on the ROBO1 in a dose-dependent manner. Our results indicate that normal crossing of the auditory pathways requires an adequate ROBO1 expression level.