Photodynamic therapy (PDT) is a promising new treatment modality for several diseases, most notably cancer. In PDT, light, O
2, and a photosensitizing drug are combined to produce a selective ...therapeutic effect. Lately, there has been active research on new photosensitizer candidates, because the most commonly used porphyrin photosensitizers are far from ideal with respect to PDT. Finding a suitable photosensitizer is crucial in improving the efficacy of PDT. Recent synthetic activity has created such a great number of potential photosensitizers for PDT that it is difficult to decide which ones are suitable for which pathological conditions, such as various cancer species. To facilitate the choice of photosensitizer, this review presents a thorough survey of the photophysical and chemical properties of the developed tetrapyrrolic photosensitizers. Special attention is paid to the singlet-oxygen yield (
Φ
Δ) of each photosensitizer, because it is one of the most important photodynamic parameters in PDT. Also, in the survey, emphasis is placed on those photosensitizers that can easily be prepared by partial syntheses starting from the abundant natural precursors, protoheme and the chlorophylls. Such emphasis is justified by economical and environmental reasons. Several of the most promising photosensitizer candidates are chlorins or bacteriochlorins. Consequently, chlorophyll-related chlorins, whose
Φ
Δ have been determined, are discussed in detail as potential photosensitizers for PDT. Finally, PDT is briefly discussed as a treatment modality, including its clinical aspects, light sources, targeting of the photosensitizer, and opportunities.
Background
Surgical treatment of ankle fracture is associated with significant pain and high postoperative opioid consumption. The anaesthesia method may affect early postoperative pain. The main ...objective of the study was to compare postoperative opioid consumption after ankle‐fracture surgery between patients treated with spinal anaesthesia and general anaesthesia.
Methods
We reviewed retrospectively the files of 586 adult patients with surgically treated ankle fracture in the years 2014 through 2016. The primary outcome was opioid consumption during the first 48 postoperative hours. Secondary outcomes were maximal pain scores, postoperative nausea and vomiting, the length of stay in the post‐anaesthesia care unit, and opioid use in different time periods up to 48 h postoperatively. Propensity score matching was used to mitigate confounding variables.
Results
Total opioid consumption 48 h postoperatively was significantly lower after spinal anaesthesia (propensity score‐matched population: effect size −13.7 milligrams; 95% CI −18.8 to −8.5; P < .001). The highest pain score on the numerical rating scale in the post‐anaesthesia care unit was significantly higher after general anaesthesia (propensity score‐matched population: effect size 3.7 points; 95% CI 3.2‐4.2; P < .001). A total of 60 patients had postoperative nausea and vomiting in the post‐anaesthesia care unit, 53 (88.3%) of whom had general anaesthesia (P = .001).
Conclusions
Patients with surgically treated ankle fracture whose operation was performed under general anaesthesia used significantly more opioids in the first 48 h postoperatively, predominantly in the post‐anaesthesia care unit, compared with patients given spinal anaesthesia.
A pneumatic tourniquet is often used during ankle fracture surgery to reduce bleeding and enhance the visibility of the surgical field. Tourniquet use causes both mechanical and ischemic pain. The ...main purpose of this study was to evaluate the effect of tourniquet time on postoperative opioid consumption after ankle fracture surgery.
We retrospectively reviewed the files of 586 adult patients with surgically treated ankle fractures during the years 2014-2016. We evaluated post hoc the effect of tourniquet time on postoperative opioid consumption during the first 24 h after surgery. The patients were divided into quartiles by the tourniquet time (4-43 min; 44-58 min; 59-82 min; and ≥83 min). Multivariable linear regression analysis was used to evaluate the results.
Tourniquets were used in 486 patients. The use of a tourniquet was associated with an increase in the total postoperative opioid consumption by 5.1 mg (95 % CI 1.6-8.5; p=0.004) during the first 24 postoperative hours. The tourniquet time over 83 min was associated with an increase in the mean postoperative oxycodone consumption by 5.4 mg (95 % CI 1.2 to 9.7; p=0.012) compared to patients with tourniquet time of 4-43 min.
The use of a tourniquet and prolonged tourniquet time were associated with higher postoperative opioid consumption during the 24 h postoperative follow-up after surgical ankle fracture fixation. The need for ethical approval and informed consent was waived by the Institutional Review Board of Northern Ostrobothnia Health District because of the retrospective nature of the study.
The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic ...disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population.
We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered.
RhD- individuals aged 40 years showed increased carotid intima-media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88).
RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).
•VIPVIZA is a pragmatic randomized controlled trial performed within the regular primary health care and targeting both individuals and physicians.•Beneficial effects on risk for cardiovascular ...disease regardless of sex and education level 3 years after providing pictorial information of subclinical atherosclerosis in addition to regular preventive information.•The results indicate that the intervention effect is a combined effect of pharmacological treatment and lifestyle modification.•The intervention effect was observed in the intermediate risk group, the group where most CVD events occur and in which sufficient prevention is often overlooked.
Non-adherence to guidelines and preventive measures is a major challenge, particularly so to obtain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years.
A Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 randomized to intervention (n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group (n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013–2016 and at follow-up after 1 and 3 years.
A beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group (p = 0.047) and SCORE was 1.69 vs. 1.82 (p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline.
This study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.
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Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset disorder with a significant impact on public health. Although a genetic contribution to risk is evident, predisposing ...genetic determinants remain largely unknown despite extensive research. So far, the most promising candidate genes have been those involved in dopamine and serotonin pathways. This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility.
We used a population sample ascertained from a birth cohort of a subpopulation of Finland, characterized by founder effect and isolation, thus minimizing genetic heterogeneity. The subjects were systematically ascertained using DSM-IV diagnostic criteria for ADHD from the Northern Finland Birth Cohort 1986 of more than 9,000 individuals, resulting in the study sample of 188 ADHD cases and 166 controls. We genotyped markers in 13 candidate genes, including critical components of dopamine and serotonin pathways.
We report evidence for association of ADHD with allelic variants of the dopamine beta-hydroxylase (DBH) and dopamine receptor D2 (DRD2) genes.
Our study supports the involvement of the dopamine pathway in the etiology of ADHD; specifically the genes DBH and DRD2 deserve more attention in further studies.
Abstract Background The aim of this study was to characterize at the population level how innate features of temperament relate to experience of depressive mood and anxiety, and whether these ...symptoms have separable temperamental backgrounds. Methods The study subjects were 4773 members of the population-based Northern Finland Birth Cohort 1966, a culturally and genetically homogeneous study sample. Temperament was measured at age 31 using the temperament items of the Temperament and Character Inventory and a separate Pessimism score. Depressive mood was assessed based on a previous diagnosis of depressive disorder or symptoms of depression according to the Hopkins Symptom Check List – 25. Anxiety was assessed analogously. Results High levels of Harm avoidance and Pessimism were related to both depressive mood (effect sizes; d = 0.84 and d = 1.25, respectively) and depressive disorder ( d = 0.68 and d = 0.68, respectively). Of the dimensions of Harm avoidance, Anticipatory worry and Fatigability had the strongest effects. Symptoms of depression and anxiety showed very similar underlying temperament patterns. Limitations Although Harm avoidance and Pessimism appear to be important endophenotype candidates for depression and anxiety, their potential usefulness as endophenotypes, and whether they meet all the suggested criteria for endophenotypes will remain to be confirmed in future studies. Conclusions Personality characteristics of Pessimism and Harm avoidance, in particular its dimensions Anticipatory worry and Fatigability, are strongly related to symptoms of depression and anxiety as well as to depressive disorder in this population. These temperamental features may be used as dimensional susceptibility factors in etiological studies of depression, which may aid in the development of improved clinical practice.
In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous ...studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Within the population‐based Finnish twin sample, FinnTwin16, we previously performed multivariate twin analyses to extract latent genetic factors, which account for the variation across seven measures of alcohol consumption (frequency of drinking, frequency × quantity, frequency of heavy drinking, frequency of intoxication and maximum drinks in a 24‐hour period) and problems (the Rutgers Alcohol Problem Index—RAPI and the Mälmö‐modified Michigan Alcohol Screen Test—MmMAST) in 3065 twins. In the present study, we examined the association between 31 DRD2/ANKK1 single‐nucleotide polymorphisms (SNPs) and the genetic factor scores generated by twin analyses in a subset of FinnTwin16 (n = 602). We focus on two of the genetic factors: a general alcohol consumption and problems factor score, which represents shared genetic variance across alcohol measures, and a alcohol problems genetic factor score, which loads onto the two indices of problematic drinking (MAST and RAPI). After correction for multiple testing across SNPs and phenotypes, of the 31 SNPs genotyped across DRD2/ANKK1, one SNP (rs10891549) showed significant association with the general alcohol consumption and problems factor score (P = 0.004), and four SNPs (rs10891549, rs1554929, rs6275, rs6279), representing two independent signals after accounting for linkage disequilibrium, showed significant association with the alcohol problems genetic factor score (P = 0.005, P = 0.005, P = 0.003, P = 0.003). In this study, we provide additional positive evidence for the association between DRD2/ANKK1 and alcohol outcomes, including frequency of drinking and drinking problems. Additionally, post hoc analyses indicate stronger association signals using genetic factor scores than individual measures, which suggest that accounting for the genetic architecture of the alcohol measures reduces genetic heterogeneity in alcohol dependence outcomes in this sample and enhances the ability to detect association.
The aims of this study were to analyze associations of dopamine receptor genes (DRD1-5) with Major Depressive Disorder (MDD) and nicotine dependence (ND), and to investigate whether ND moderates ...genetic influences on MDD.
The sample was ascertained from the Finnish Twin Cohort. Twin pairs concordant for smoking history were recruited along with their family members, as part of the multisite Nicotine Addiction Genetics consortium. Genetic association analyses were based on 1428 adults. Total of 70 tagging single nucleotide polymorphisms within the dopamine receptor genes were genotyped and analyzed for association with MDD, ND, and MD-ND co-morbidity. Individual level logistic regression analyses were based on 1296 adults with data on ND and MDD diagnoses, as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use. Four independent samples, such as population-based and case-control samples, were used for replication.
Rs2399496, located 1.5 kb downstream of DRD3, showed suggestive association for MDD (p = 0.00076) and significant association for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND-interaction justified analyses by genetic risk variant and ND status. Individuals with ND and two minor alleles (AA) of rs2399496 had almost six-fold risk for MDD (OR 5.74, 95%CI 3.12-10.5, p = 9.010e-09) compared to individuals without ND and with two major alleles (TT).
Significant association between a variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our results further suggest that nicotine dependence may potentiate the influence of the DRD3 genetic variant on MDD.
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