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.
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.
Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a significant public-health impact. Previously, we described a candidate gene study in a ...population-based birth cohort that demonstrated an association with ADHD-affected males and the dopamine receptor D2 (DRD2). The current study evaluates potential associations of dopamine receptor genes and Cloninger temperament traits within this same sample. Participants with stringent lifetime ADHD diagnoses were ascertained systematically from the genetically isolated Northern Finland 1986 Birth Cohort (n=9432), resulting in 178 cases and 157 controls. Markers in all known dopamine receptor genes were genotyped. We report an association of DRD2 with low Persistence in females (rs1079727 P=0.02, rs1124491 P=0.02, rs1800497 P=0.03). The associated DRD2 minor allelic haplotype (CAA, P=0.03) is the same haplotype we previously associated with ADHD in males in this birth cohort. The current study further supports previous results on the role of DRD2 in individuals with ADHD. Investigations suggest that DRD2 may have an impact on both males and females, but the particular outcome appears sex-specific, manifesting as ADHD in males and low Persistence in females. Furthermore, these findings suggest that the putative role of low Persistence as an endophenotype for ADHD deserves further investigation.
ObjectivesDepression is a worldwide leading cause of morbidity and disability. Genetic studies have recently begun to elucidate its molecular aetiology. The authors investigated candidate genes of ...monoamine neurotransmission and early environmental risk factors for depressiveness in the genetically isolated population-based Northern Finland Birth Cohort 1966 (12 058 live births).DesignThe authors ascertained and subdivided the study sample (n=5225) based on measures of early development and of social environment, and examined candidate genes of monoamine neurotransmission, many of which have shown prior evidence of a gene–environment interaction for affective disorders, namely SLC6A4, TPH2, COMT, MAOA and the dopamine receptor genes DRD1–DRD5.Results and conclusionThe authors observed no major genetic effects of the analysed variants on depressiveness. However, when measures of early development and of social environment were considered, some evidence of interaction was observed. Allelic variants of COMT interacted with high early developmental risk (p=0.005 for rs2239393 and p=0.02 for rs4680) so that the association with depression was detected only in individuals at high developmental risk group (p=0.0046 and β=0.056 for rs5993883–rs2239393–rs4680 risk haplotype CGG including Val158), particularly in males (p=0.0053 and β=0.083 for the haplotype CGG). Rs4274224 from DRD2 interacted with gender (p=0.017) showing a significant association with depressiveness in males (p=0.0006 and β=0.0023; p=0.00005 and β=0.069 for rs4648318–rs4274224 haplotype GG). The results support the role of genes of monoamine neurotransmission in the aetiology of depression conditional on environmental risk and sex, but not direct major effects of monoaminergic genes in this unselected population.
Tiivistelmä. Nilkkamurtumat ovat yleisin työikäisten murtuma, joka vaatii sairaala- ja leikkaushoitoa. Näiden murtumien määrä on kasvussa väestön ikääntymisen myötä. Instabiilit nilkkamurtumat ...hoidetaan leikkaushoidolla, jotta murtuneet kehräsluut voidaan palauttaa anatomiseen asentoonsa. Leikkauksissa anestesiavaihtoehtoina ovat yleis- tai spinaalianestesia ja molempiin muotoihin liittyvät omat etunsa ja haittansa. Tämän vuoksi anestesiamuodon valinnassa on huomioitava potilaan tilanne kokonaisuutena.
Ortopedisiin leikkauksiin, kuten nilkkamurtumaleikkauksiin, liittyy voimakasta leikkauksen jälkeistä kipua, mikä voi muodostua ongelmaksi leikkauksen jälkeen potilaan toipumisen ja mobilisaation kannalta. Usein leikkauksen jälkeinen kipu hoidetaan opioidilääkityksellä. Tämä tutkimus on retrospektiivinen tutkimus, jonka aineistona käytettiin vuonna 2016 Oulun Yliopistollisessa sairaalassa leikattuja aikuisia nilkkamurtumapotilaita, joille oli tehty toimenpidekoodin NHJ10 mukainen kiinnitysleikkaus. Aineisto kerättiin ESKO-potilastietojärjestelmästä tutkittavan potilaskertomuksen ja anestesiakertomuksen perusteella. Aineistomääräksi saatiin 166 potilasta.
Tutkimuksen tarkoituksena oli kartoittaa nilkkamurtumapotilaiden leikkaushoitoon liittyviä tekijöitä ja menetelmiä, mitkä vaikuttavat leikkauksen jälkeiseen akuuttiin kipuun ja opioidikulutukseen. Tärkeimpinä arvioinnin kohteena olivat anestesiamuodon ja leikkausmenetelmän yhteys leikkauksen jälkeiseen opioidilääkityksen määrään ja sairaalassa oloaikaan. Eri tekijöiden vertailussa käytettiin tilastollista analyysia, jolla selvitettiin tekijöiden merkityksellisyyttä.
Tutkimuksen perusteella spinaalianestesian saannet potilaat olivat kivuttomampia leikkauksen jälkeen ja heidän opioidilääkitysen määrä heräämössä ja leikkauspäivänä oli puolet pienempi kuin yleisanestesian saaneilla potilailla. Sairaalassa oloaikaan vaikuttivat vammanlaajuus ja leikkaustekniikka. Nilkkamurtumia esiintyi aineistossamme korostuneesti ikääntyvässä väestössä erityisesti naisilla. Leikkaushoitoon liittyviä komplikaatioita olivat haavainfektiot, joille altistavat alkoholin käyttö, diabetes, runsaat perussairaudet ja vammalaajuus.
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.
Residual problems may occur from neuroma despite surgery. In a 12-month follow-up study using national register data, symptoms, and disabilities related to surgical methods and sex were evaluated in ...patients surgically treated for a neuroma. Among 196 identified patients (55% men; lower age; preoperative response rate 20%), neurolysis for nerve tethering/scar formation was the most used surgical method (41%; more frequent in women) irrespective of affected nerve. Similar preoperative symptoms were seen in patients, where different surgical methods were performed. Pain on load was the dominating symptom preoperatively. Women scored higher preoperatively at pain on motion without load, weakness and QuickDASH. Pain on load and numbness/tingling in fingers transiently improved. The ability to perform daily activities was better after nerve repair/reconstruction/transposition than after neurolysis. Regression analysis, adjusted for age, sex, and affected nerve, showed no association between surgical method and pain on load, tingling/numbness in fingers, or ability to perform daily activities. Neuroma, despite surgery, causes residual problems, affecting daily life. Choice of surgical method is not strongly related to pre- or postoperative symptoms. Neurolysis has similar outcome as other surgical methods. Women have more preoperative symptoms and disabilities than men. Future research would benefit from a neuroma-specific ICD-code, leading to a more precise identification of patients.
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•We review interventions to reduce cognitive decline.•We include studies in people without dementia, aged 50+ or with cognitive impairment.•4+ months of twice weekly exercise improved ...memory or global cognition.•4+ months of more cognitively challenging exercise improved memory/global cognition.•Some intervention effects were sustained up to a year beyond facilitated sessions.
It is unclear what non-pharmacological interventions to prevent cognitive decline should comprise. We systematically reviewed lifestyle and psychosocial interventions that aimed to reduce cognitive decline in healthy people aged 50+, and people of any age with Subjective Cognitive Decline or Mild Cognitive Impairment. We narratively synthesised evidence, prioritising results from studies rated as at lower Risk of Bias (ROB) and assigning Centre for Evidence Based Medicine grades. We included 64 papers, describing: psychosocial (n = 12), multi-domain (n = 10), exercise (n = 36), and dietary (n = 6) interventions. We found Grade A evidence that over 4+ months: aerobic exercise twice weekly had a moderate effect on global cognition in people with/ without MCI; and interventions that integrate cognitive and motor challenges (e.g. dance, dumb bell training) had small to moderate effects on memory or global cognition in people with MCI. We found Grade B evidence that 4+ months of creative art or story-telling groups in people with MCI; 6 months of resistance training in people with MCI and a two-year, dietary, exercise, cognitive training and social intervention in people with or without MCI had small, positive effects on global cognition. Effects for some intervention remained up to a year beyond facilitated sessions.
Pain, and disabilities after neuroma surgery, using patient reported outcome measurements (PROMs), were evaluated by QuickDASH and a specific Hand Questionnaire (HQ-8). The 69 responding individuals ...(response rate 61%; 59% women; 41% men; median follow up 51 months) reported high QuickDASH score, pain on load, cold sensitivity, ability to perform daily activities and sleeping difficulties. Individuals reporting impaired ability to perform daily activities and sleeping problems had higher scores for pain, stiffness, weakness, numbness/tingling, cold sensitivity and QuickDASH. Only 17% of individuals reported no limitations at all. No differences were observed between sexes. Surgical methods did not influence outcome. Symptoms and disabilities correlated moderately-strongly to each other and to ability to perform regular daily activities as well as to sleeping difficulties. Pain, cold sensitivity, sleeping difficulties and limitation to perform daily activities were associated to higher QuickDASH. A weak association was found between follow up time and QuickDASH score as well as pain on load, but not cold sensitivity. A major nerve injury was frequent among those with limitations during work/performing other regular daily activities. Despite surgical treatment, neuromas cause residual problems, which affect the capacity to perform daily activities and ability to sleep with limited improvement in long-term.
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