Comparative genomics provides insights into the aquatic adaptations of mammals.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

Evidence of unidirectional hybridization and second-generation adult hybrid between the two largest animals on Earth, the fin and blue whales.

Biodiversity in the oceans has dramatically declined since the beginning of the industrial era, with accelerated loss of marine biodiversity impairing the ocean's capacity to maintain vital ecosystem services. A few organisms epitomize the damaging and long-lasting effects of anthropogenic exploitation: Some whale species, for instance, were brought to the brink of extinction, with their population sizes reduced to such low levels that may have caused a significant disruption to their reproductive dynamics and facilitated hybridization events. The incidence of hybridization is nevertheless believed to be rare, and very little information exists on its directionality. Here, using genetic markers, we show that all but one whale hybrid sample collected in Icelandic waters originated from the successful mating of male fin whale and female blue whale, thus suggesting unidirectional hybridization. We also demonstrate for the first time the existence of a second-generation adult (male) hybrid resulting from a backcross between a female hybrid and a pure male fin whale. The incidence of hybridization events between fin and blue whales is likely underestimated and the observed unidirectional hybridization (for F1 and F2 hybrids) is likely to induce a reproductive loss in blue whale, which may represent an additional challenge to its recovery in the Atlantic Ocean compared to other rorquals.

Blame it on the weather? The association between pain in fibromyalgia, relative humidity, temperature and barometric pressure.

Self-reported pain levels in patients with fibromyalgia may change according to weather conditions. Previous studies suggest that low barometric pressure (BMP) is significantly related to increased pain, but that the contribution of changes in BMP has limited clinical relevance. The present study examined whether BMP influenced variability in perceived stress, and if stress levels moderated or mediated the relationship between BMP and pain. Forty-eight patients with fibromyalgia enrolled in a randomized controlled trail (RCT) reported pain and emotional state three times daily with mobile phone messages for a 30-consecutive day period prior to the start of the treatment in the RCT. The patients were unaware that weather data were collected simultaneously with pain and emotional reports. The results showed that lower BMP and increased humidity were significantly associated with increased pain intensity and pain unpleasantness, but only BMP was associated with stress levels. Stress levels moderated the impact of lower BMP on pain intensity significantly, where higher stress was associated with higher pain. Significant individual differences were present shown by a sub-group of patients (n = 8) who reacted opposite compared to the majority of patients (n = 40) with increased pain reports to an increase in BMP. In sum, lower BMP was associated with increased pain and stress levels in the majority of the patients, and stress moderated the relationship between BMP and pain at the group-level. Significant individual differences in response to changes in BMP were present, and the relation between weather and pain may be of clinical relevance at the individual level.

Complete Inactivation of Sebum-Producing Genes Parallels the Loss of Sebaceous Glands in Cetacea.

Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of "gene vestiges" in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.

Leave or stay? Video-logger revealed foraging efficiency of humpback whales under temporal change in prey density.

Central place foraging theory (CPF) has been used to predict the optimal patch residence time for air-breathing marine predators in response to patch quality. Humpback whales (Megaptera novaeangliae) forage on densely aggregated prey, which may induce drastic change in prey density in a single feeding event. Thus, the decision whether to leave or stay after each feeding event in a single dive in response to this drastic change, should have a significant effect on prey exploitation efficiency. However, whether humpback whales show adaptive behavior in response to the diminishing prey density in a single dive has been technically difficult to test. Here, we studied the foraging behavior of humpback whales in response to change in prey density in a single dive and calculated the efficiency of each foraging dive using a model based on CPF approach. Using animal-borne accelerometers and video loggers attached to whales, foraging behavior and change in relative prey density in front of the whales were successfully quantified. Results showed diminishing rate of energy intake in consecutive feeding events, and humpback whales efficiently fed by bringing the rate of energy intake close to maximum in a single dive cycle. This video-based method also enabled us to detect the presence of other animals around the tagged whales, showing an interesting trend in behavioral changes where feeding duration was shorter when other animals were present. Our results have introduced a new potential to quantitatively investigate the effect of other animals on free-ranging top predators in the context of optimal foraging theory.

Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis.

BACKGROUND: The evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear. METHODS: Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, 'active' placebo, or no intervention in adult participants with major depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library's CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency until January 2016. All data were extracted by at least two independent investigators. We used Cochrane systematic review methodology, Trial Sequential Analysis, and calculation of Bayes factor. An eight-step procedure was followed to assess if thresholds for statistical and clinical significance were crossed. Primary outcomes were reduction of depressive symptoms, remission, and adverse events. Secondary outcomes were suicides, suicide attempts, suicide ideation, and quality of life. RESULTS: A total of 131 randomised placebo-controlled trials enrolling a total of 27,422 participants were included. None of the trials used 'active' placebo or no intervention as control intervention. All trials had high risk of bias. SSRIs significantly reduced the Hamilton Depression Rating Scale (HDRS) at end of treatment (mean difference -1.94 HDRS points; 95% CI -2.50 to -1.37; P < 0.00001; 49 trials; Trial Sequential Analysis-adjusted CI -2.70 to -1.18); Bayes factor below predefined threshold (2.01*10-23). The effect estimate, however, was below our predefined threshold for clinical significance of 3 HDRS points. SSRIs significantly decreased the risk of no remission (RR 0.88; 95% CI 0.84 to 0.91; P < 0.00001; 34 trials; Trial Sequential Analysis adjusted CI 0.83 to 0.92); Bayes factor (1426.81) did not confirm the effect). SSRIs significantly increased the risks of serious adverse events (OR 1.37; 95% CI 1.08 to 1.75; P = 0.009; 44 trials; Trial Sequential Analysis-adjusted CI 1.03 to 1.89). This corresponds to 31/1000 SSRI participants will experience a serious adverse event compared with 22/1000 control participants. SSRIs also significantly increased the number of non-serious adverse events. There were almost no data on suicidal behaviour, quality of life, and long-term effects. CONCLUSIONS: SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013004420.

Sexual Abuse of Older Residents in Nursing Homes: A Focus Group Interview of Nursing Home Staff.

The objective of this study was to increase knowledge of sexual abuse against older residents in nursing homes. A qualitative approach was used. Through a focus group interview with staff in nursing homes, the aim was to reveal employees' thoughts, experiences, and attitudes. Findings from the focus group interview show that sexual abuse of older residents is a taboo topic among health professionals. Acts of sexual abuse are difficult to imagine; it is hard to believe that it occurs. The fact that staff are not aware that it could happen, or have a hard time believing that it actually happens, can amplify the residents' vulnerable position as potential victims of abuse, and it makes it even more challenging to report or uncover such acts. The study highlights the need for education of all health care workers in Norway as well as more research on sexual abuse against older residents in nursing homes. Furthermore, there is a need for good policies and reporting systems, as an important step towards addressing sexual abuse of the aged in a more appropriate way. Further research must aim to reveal more about this taboo area.

Sexual abuse of older nursing home residents: a literature review.

Despite an increasing literature related to elder abuse, sexual abuse of older persons in general and of vulnerable adults living in nursing homes in particular is still sparsely described. The purpose of this study was to assess the state of knowledge on the subject of sexual abuse against older nursing home residents through a literature review. Systematic searches in reference databases including Cinahl, Medline, OVID Nursing Database, ISI Web of Science, PsycINFO, Cochrane Library, and SveMed + were conducted. Through several phases of selection of the articles, using strict inclusion and exclusion criteria, six articles were chosen for a deeper examination. Findings from the review show that sexual abuse occurs in nursing homes and that both older women and men are victims of sexual abuse. Perpetrators appear mainly to be staff and other residents and mainly to be men, but also women abuse both older men and older women. Findings from the literature review show that there is a need for knowledge and further research on the topic of sexual abuse against older residents in nursing homes. Furthermore, there is a need for good policies and reporting systems, as an important step in seriously addressing sexual abuse against older persons.

[Squamous cell carcinoma in ulcer after bacille Calmette-Guérin vaccination].

Marjolin's ulcer is an aggressive squamous cell carcinoma (SCC) found in chronically inflamed skin. SCC has been reported in smallpox vaccination sites, whereas basal cell carcinomas are more common in scar after bacille Calmette-Guérin (BCG) vaccination. A 72-year-old man presented with a chronic ulcer at the site of his childhood BCG vaccination. At the time of examination, a 3 × 1.5 cm fleshy and secreting ulcer was found on the shoulder. Biopsy revealed SCC, and the tumour was surgically removed. In conclusion, chronic ulcers, especially those originating in chronically inflamed skin, should be regularly biopsied to assure that malignant transformation has not occurred.

Acoustically invisible feeding blue whales in Northern Icelandic waters.

Fixed passive acoustic monitoring can be used for long-term recording of vocalizing cetaceans. Both presence monitoring and animal density estimation requires the call rates and sound source levels of vocalizations produced by single animals. In this study, blue whale calls were recorded using acoustic bio-logging systems in Skjálfandi Bay off Húsavík, Northeast Iceland, in June 2012. An accelerometer was attached to individual whales to monitor diving behavior. During 21 h recording two individuals, 8 h 45 min and 13 h 2 min, respectively, 105 and 104 lunge feeding events and four calls were recorded. All recorded calls were down-sweep calls ranging from 105 to 48 Hz. The sound duration was 1-2 s. The source level was estimated to be between 158 and 169 dB re 1µPa rms, assuming spherical sound propagation from the possible sound source location to the tag. The observed sound production rates and source levels of individual blue whales during feeding were extremely small compared with those observed previously in breeding grounds. The feeding whales were nearly acoustically invisible. The function of calls during feeding remains unknown.

West Greenland harbour porpoises assayed for antibodies against Toxoplasma gondii: false positives with the direct agglutination method.

We assayed blood/tissue fluid samples from 20 harbour porpoises Phocoena phocoena from western Greenland coastal waters for antibodies against the protozoan parasite Toxoplasma gondii by the direct agglutination test (DAT). Nine individuals (45%) were interpreted to be seropositive at 1:40 dilution and 4 (20%) were seropositive up to 1:160. Samples from these individuals were assayed by an enzyme-linked immunosorbent assay (ELISA), and tissue samples of the DAT-positive animals were tested by a nested polymerase chain reaction (nPCR). Results from both methods were negative, suggesting the absence of infection in the tested animals. After chloroform clean-up, all were negative when re-assayed by DAT. We concluded that infection with T. gondii was absent in all 20 animals, despite the initially positive DAT results, and that the false positives resulted from non-specific adherence to tachyzoites in the DAT assay which could be removed by the chloroform clean-up method. Our results suggest that detecting antibodies against T. gondii using the DAT or the modified agglutination technique, particularly on samples from Arctic marine animals which often are rich in lipids, may lead to false positive results. For such samples, the use of ELISA or PCR on available tissue samples may be advocated as confirmatory tests in order to avoid false positives and overestimating seroprevalence.

[Children with infantile haemangiomas should be worked-up for PHACE syndrome]. / Børn med store faciale hæmangiomer bør udredes for PHACE-syndrom.

Infantile haemangiomas are the most common tumours in infants. Large facial haemangiomas are associated with posterior fossa malformations, haemangiomas, arteriel malformations, cardiac defects and eye anomalies (PHACE) syndrome in 20-31%. The diagnosis requires a large facial haemangiom and the minimum of one extracutaneous manifestation. Infants with large facial haemangiomas are in risk of PHACE syndrome and need to be referred to paediatric expertise. This case represents an infant with a large facial haemangioma, who was diagnosed with a coarctatio aortae and hence the PHACE syndrome.

Aetiology, treatment and mortality after oesophageal perforation in Denmark.

INTRODUCTION: Perforation of the oesophagus into the thoracic cavity is a potentially life-threatening condition. The causes are numerous. Treatment for oesophageal perforation targets mediastinal and pleural contamination. Present knowledge about the causes of perforation and the types of treatment is poor. MATERIAL AND METHODS: A retrospective review was made between 1997 and 2005 based on extracts from the National Patient Registry. RESULTS: A total of 286 patients were diagnosed with perforation of the oesophagus (131 women and 155 men). Their average age was 60 years. A wide spectrum of causes was reported, e.g. instrumentation of the oesophagus 136 (47.6%), spontaneous rupture 89 (31.1%) or procedures otherwise related to surgical intervention 9 (3.1%). One third of the patients started conservative treatment 91 (31.9%). The majority of the patients were transferred to a thoracic surgery department for further treatment: about 25% of patients underwent surgery. The average hospitalization time was 18 days. The mortality rate was 21%. CONCLUSION: Oesophageal perforation remains a diagnostic and therapeutic challenge and the condition requires aggressive treatment. Recent consensus in early treatment with thoracotomy, debridement, irrigation and subsequent parenteral nutrition has improved survival. In this material, most perforations were iatrogenic in nature. In the 2002-2005 period, the study showed that 29% of the iatrogenic perforations were caused by the use of a rigid endoscope which is risky and whose use should therefore be restricted. It is advisable to set up national guidelines for treatment of oesophageal perforation and to centralise treatment.

Caspase-5 expression is upregulated in lesional psoriatic skin.

The inflammasome is a cytosolic multiprotein complex with two major functions: recognizing pathogen-associated molecular patterns and reacting to these through activation of the proinflammatory cytokines IL-1ß and IL-18. In this study, we characterized the expression of inflammasome components in psoriatic skin and other common inflammatory skin diseases. Human skin biopsy specimens, cultured primary human keratinocytes, and peripheral blood mononuclear cells (PBMCs) were analyzed using quantitative reverse transcriptase-PCR (RT-PCR) and semiquantitative western blotting. mRNA expression of the inflammasome components NALP1, NALP3, ASC, caspase-1, caspase-4, and caspase-5 was detected in psoriatic skin. Interestingly, we found an extensive, 20-fold upregulation (P<0.01) of caspase-5 mRNA in lesional compared with nonlesional psoriatic skin, whereas caspase-1, caspase-4, and ASC (apoptosis-associated speck-like protein with CARD domain) mRNAs were upregulated by only 1.5- to 2.6-fold (P<0.01). Caspase-5 mRNA was not increased in biopsies from other inflammatory skin diseases, suggesting that this finding could be psoriasis specific. In vitro experiments revealed that caspase-5 mRNA was induced in primary keratinocytes as well as PBMCs stimulated with IFN-γ. Inhibition studies suggested that caspase-5 mRNA upregulation was mediated through the NF-κB pathway. Our findings suggest that caspase-5 and the inflammasome may have an important role in the inflammatory response in psoriasis.

Harbour porpoises respond to climate change.

The effects of climate change on marine ecosystems and in particular on marine top predators are difficult to assess due to, among other things, spatial variability, and lack of clear delineation of marine habitats. The banks of West Greenland are located in a climate sensitive area and are likely to elicit pronounced responses to oceanographic changes in the North Atlantic. The recent increase in sea temperatures on the banks of West Greenland has had cascading effects on sea ice coverage, residency of top predators, and abundance of important prey species like Atlantic cod (Gadus morhua). Here, we report on the response of one of the top predators in West Greenland; the harbour porpoise (Phocoena phocoena). The porpoises depend on locating high densities of prey species with high nutritive value and they have apparently responded to the general warming on the banks of West Greenland by longer residence times, increased consumption of Atlantic cod resulting in improved body condition in the form of larger fat deposits in blubber, compared to the situation during a cold period in the 1990s. This is one of the few examples of a measurable effect of climate change on a marine mammal population.

[Need for a national database on lumbar fusion surgery]. / Behov for national database ved operation for lumbal spondylodese.

INTRODUCTION: The indication for surgical technique in lumbar fusion is debated. The objective of this study was to analyse the indication and operative technique in lumbar surgery clinics in Denmark. MATERIAL AND METHODS: A cohort study based on a sample from four public and four private clinics in 2006 was used. RESULTS: There was no difference in patient demographics and diagnosis between public and private clinics. In 62% of the patient files, information was lacking. Considerations on indication and surgery did not differ from public to private clinics. A standard preoperative rehabilitation program was performed in 59% of the cases. Combined anterior and posterior fusion was performed in 37 cases, posterior instrumented fusion in 77 cases and posterior uninstrumented fusion in 105 cases, interspinous spacer was used in six cases and disc arthroplasty in 13 cases. CONCLUSION: Adequate evaluation of indication and choice of surgical technique in lumbar fusion based on patient files was not possible. We found no qualitative differences between public and private clinics. A national database is needed to monitor indication and choice of operative procedure.

[Pancreaticoduodenectomy in Denmark 2005-2008]. / Pankreatikoduodenektomi i Danmark 2005-2008.

INTRODUCTION: Pancreaticoduodenectomy (PD) is associated with high mortality and morbidity. Results can be optimised through centralisation and adjustment of perioperative care. The aim of this study was to describe organisation, postoperative stay, readmission and hospital mortality in the period 2005-2008 and to evaluate postoperative care and treatment after PD in 2007-2008. MATERIAL AND METHODS: The study is based on data from the National Patient Registry for the period 2005-2008 and medical records for 2007-2008 from PD patients. RESULTS: The median duration of postoperative stay in hospital 2005-2008 was 17 days (range 2-649). The readmission rate was 11%, and hospital mortality was 6%. In 2007-2008, both wound infections and intraabdominal abscesses were seen in 12% of cases, and anastomotic leakage of the hepaticojejunostomy and pancreaticojejunostomy occurred in 9% and 12% of cases, respectively. Four percent had no wound-related complications. Nasogastric and nasojejunal tubes were removed postoperatively on median day five and day six, respectively. Clear fluid intake began from median day five and solid food from day seven. The epidural catheter was removed on median day five and abdominal drains on day seven. CONCLUSION: Mortality and postoperative hospital stay after PD were reduced in Denmark from the period 1996-2004 to 2005-2008, but the morbidity remains high. The results suggest a need for adjustment of perioperative care to current evidence-based care standards.

A Characterization of the expression of 14-3-3 isoforms in psoriasis, basal cell carcinoma, atopic dermatitis and contact dermatitis.

14-3-3 is a highly conserved protein involved in a number of cellular processes including cell signalling, cell cycle regulation and gene transcription. Seven isoforms of the protein have been identified; ß, γ, ε, ζ η σ and τ. The expression profile of the various isoforms in skin diseases is unknown. To investigate the expression of the seven 14-3-3 isoforms in involved and uninvolved skin from psoriasis, basal cell carcinoma (BCC), atopic dermatitis and nickel induced allergic contact dermatitis. Punch biopsies from involved and uninvolved skin were analyzed with quantitative reverse transcription-polymerase chain reaction to determine the mRNA expression of the 14-3-3 isoforms. The protein level of 14-3-3 isoforms was measured by Western blot technique in keratome biopsies from patients with psoriasis. Evaluation of dermal and epidermal protein expression was performed by immunofluorescence staining. Increased 14-3-3τ mRNA levels were detected in involved skin from patients with psoriasis, contact dermatitis and BCC. 14-3-3σ mRNA expression was increased in psoriasis and contact dermatitis, but not in BCC. In atopic dermatitis no significant difference between involved and uninvolved skin was found. The expression of the 14-3-3 isoforms was also studied at the protein level in psoriasis. Only 14-3-3τ expression was significantly increased in involved psoriatic skin compared with uninvolved skin. Immunofluorescence staining with 14-3-3τ- and 14-3-3σ-specific antibodies showed localization of both isoforms to the cytoplasm of the keratinocytes in the various skin sections. These results demonstrate a disease specific expression profile of the 14-3-3τ and 14-3-3σ iso-forms.

[Lumbar fusion surgery for degenerative conditions in Denmark 2005-2006]. / Lumbal spondylodese for degenerativ ryglidelse i Danmark i 2005-2006.

INTRODUCTION: The indication and use of lumbar spinal fusion surgery for degenerative conditions is being debated. PURPOSE: The objective of this study was to describe recent trends in lumbar fusion surgery for degenerative conditions in Denmark. MATERIAL AND METHODS: A cohort study using a sample from the Danish National Patient Registry was used. RESULTS: In 2005 and 2006, 2,064 and 891 lumbar fusions were performed in 14 public and 6 private hospitals. The annual activity increased from 993 to 1,118 procedures at public hospitals and from 393 to 510 procedures at private hospitals. Lumbar disc arthroplasty was performed in 196 cases, anterior fusion in 162 case, posterior fusion in 2,309 cases, while combined anterior and posterior fusion were performed in 347 cases. The indications for surgery were based on the diagnosis spondylosis in 245 cases, spinal stenosis in 1,174 cases, discuss degeneration in 947 cases, degenerative spondylolisthesis in 600 cases and non-specific lumbar pain in 45 cases. Posterior fusion was performed in 74.3% and 81.9% in public and private hospitals, respectively. Combined anterior and posterior fusion was performed in 12.1% and 10.1% in public and private hospitals, respectively. CONCLUSION: Lumbar fusion rates for degenerative conditions increased from 2005 to 2006 with variation in operative procedures in relation to diagnoses. We propose to monitor data in a database to improve registration of various fusion techniques for various indications and to support further research.