The effect of tourniquet use on postoperative opioid consumption after ankle fracture surgery - a retrospective cohort study.

OBJECTIVES: 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. METHODS: 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. 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. CONCLUSIONS: 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.

Difference in postoperative opioid consumption after spinal versus general anaesthesia for ankle fracture surgery-A retrospective cohort study.

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.

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

A Linkage-Based Genome Assembly for the Mosquito Aedes albopictus and Identification of Chromosomal Regions Affecting Diapause.

The Asian tiger mosquito, Aedes albopictus, is an invasive vector mosquito of substantial public health concern. The large genome size (~1.19-1.28 Gb by cytofluorometric estimates), comprised of ~68% repetitive DNA sequences, has made it difficult to produce a high-quality genome assembly for this species. We constructed a high-density linkage map for Ae. albopictus based on 111,328 informative SNPs obtained by RNAseq. We then performed a linkage-map anchored reassembly of AalbF2, the genome assembly produced by Palatini et al. (2020). Our reassembled genome sequence, AalbF3, represents several improvements relative to AalbF2. First, the size of the AalbF3 assembly is 1.45 Gb, almost half the size of AalbF2. Furthermore, relative to AalbF2, AalbF3 contains a higher proportion of complete and single-copy BUSCO genes (84.3%) and a higher proportion of aligned RNAseq reads that map concordantly to a single location of the genome (46%). We demonstrate the utility of AalbF3 by using it as a reference for a bulk-segregant-based comparative genomics analysis that identifies chromosomal regions with clusters of candidate SNPs putatively associated with photoperiodic diapause, a crucial ecological adaptation underpinning the rapid range expansion and climatic adaptation of A. albopictus.

Clustering of loci controlling species differences in male chemical bouquets of sympatric Heliconius butterflies.

The degree to which loci promoting reproductive isolation cluster in the genome-that is, the genetic architecture of reproductive isolation-can influence the tempo and mode of speciation. Tight linkage between these loci can facilitate speciation in the face of gene flow. Pheromones play a role in reproductive isolation in many Lepidoptera species, and the role of endogenously produced compounds as secondary metabolites decreases the likelihood of pleiotropy associated with many barrier loci. Heliconius butterflies use male sex pheromones to both court females (aphrodisiac wing pheromones) and ward off male courtship (male-transferred antiaphrodisiac genital pheromones), and it is likely that these compounds play a role in reproductive isolation between Heliconius species. Using a set of backcross hybrids between H. melpomene and H. cydno, we investigated the genetic architecture of putative male pheromone compound production. We found a set of 40 significant quantitative trait loci (QTL) representing 33 potential pheromone compounds. QTL clustered significantly on two chromosomes, chromosome 8 for genital compounds and chromosome 20 for wing compounds, and chromosome 20 was enriched for potential pheromone biosynthesis genes. There was minimal overlap between pheromone QTL and known QTL for mate choice and color pattern. Nonetheless, we did detect linkage between a QTL for wing androconial area and optix, a color pattern locus known to play a role in reproductive isolation in these species. This tight clustering of putative pheromone loci might contribute to coincident reproductive isolating barriers, facilitating speciation despite ongoing gene flow.

A major locus controls a biologically active pheromone component in Heliconius melpomene.

Understanding the production, response, and genetics of signals used in mate choice can inform our understanding of the evolution of both intraspecific mate choice and reproductive isolation. Sex pheromones are important for courtship and mate choice in many insects, but we know relatively little of their role in butterflies. The butterfly Heliconius melpomene uses a complex blend of wing androconial compounds during courtship. Electroantennography in H. melpomene and its close relative Heliconius cydno showed that responses to androconial extracts were not species specific. Females of both species responded equally strongly to extracts of both species, suggesting conservation of peripheral nervous system elements across the two species. Individual blend components provoked little to no response, with the exception of octadecanal, a major component of the H. melpomene blend. Supplementing octadecanal on the wings of octadecanal-rich H. melpomene males led to an increase in the time until mating, demonstrating the bioactivity of octadecanal in Heliconius. Using quantitative trait locus (QTL) mapping, we identified a single locus on chromosome 20 responsible for 41% of the parental species' difference in octadecanal production. This QTL does not overlap with any of the major wing color or mate choice loci, nor does it overlap with known regions of elevated or reduced FST . A set of 16 candidate fatty acid biosynthesis genes lies underneath the QTL. Pheromones in Heliconius carry information relevant for mate choice and are under simple genetic control, suggesting they could be important during speciation.

First High-Density Linkage Map and Single Nucleotide Polymorphisms Significantly Associated With Traits of Economic Importance in Yellowtail Kingfish Seriola lalandi.

The genetic resources available for the commercially important fish species Yellowtail kingfish (YTK) (Seriola lalandi) are relative sparse. To overcome this, we aimed (1) to develop a linkage map for this species, and (2) to identify markers/variants associated with economically important traits in kingfish (with an emphasis on body weight). Genetic and genomic analyses were conducted using 13,898 single nucleotide polymorphisms (SNPs) generated from a new high-throughput genotyping by sequencing platform, Diversity Arrays Technology (DArTseqTM) in a pedigreed population comprising 752 animals. The linkage analysis enabled to map about 4,000 markers to 24 linkage groups (LGs), with an average density of 3.4 SNPs per cM. The linkage map was integrated into a genome-wide association study (GWAS) and identified six variants/SNPs associated with body weight (P < 5e-8) when a multi-locus mixed model was used. Two out of the six significant markers were mapped to LGs 17 and 23, and collectively they explained 5.8% of the total genetic variance. It is concluded that the newly developed linkage map and the significantly associated markers with body weight provide fundamental information to characterize genetic architecture of growth-related traits in this population of YTK S. lalandi.

No evidence for maintenance of a sympatric Heliconius species barrier by chromosomal inversions.

Mechanisms that suppress recombination are known to help maintain species barriers by preventing the breakup of coadapted gene combinations. The sympatric butterfly species Heliconius melpomene and Heliconius cydno are separated by many strong barriers, but the species still hybridize infrequently in the wild, and around 40% of the genome is influenced by introgression. We tested the hypothesis that genetic barriers between the species are maintained by inversions or other mechanisms that reduce between-species recombination rate. We constructed fine-scale recombination maps for Panamanian populations of both species and their hybrids to directly measure recombination rate within and between species, and generated long sequence reads to detect inversions. We find no evidence for a systematic reduction in recombination rates in F1 hybrids, and also no evidence for inversions longer than 50 kb that might be involved in generating or maintaining species barriers. This suggests that mechanisms leading to global or local reduction in recombination do not play a significant role in the maintenance of species barriers between H. melpomene and H. cydno.

cgDNA: a software package for the prediction of sequence-dependent coarse-grain free energies of B-form DNA.

cgDNA is a package for the prediction of sequence-dependent configuration-space free energies for B-form DNA at the coarse-grain level of rigid bases. For a fragment of any given length and sequence, cgDNA calculates the configuration of the associated free energy minimizer, i.e. the relative positions and orientations of each base, along with a stiffness matrix, which together govern differences in free energies. The model predicts non-local (i.e. beyond base-pair step) sequence dependence of the free energy minimizer. Configurations can be input or output in either the Curves+ definition of the usual helical DNA structural variables, or as a PDB file of coordinates of base atoms. We illustrate the cgDNA package by comparing predictions of free energy minimizers from (a) the cgDNA model, (b) time-averaged atomistic molecular dynamics (or MD) simulations, and (c) NMR or X-ray experimental observation, for (i) the Dickerson-Drew dodecamer and (ii) three oligomers containing A-tracts. The cgDNA predictions are rather close to those of the MD simulations, but many orders of magnitude faster to compute. Both the cgDNA and MD predictions are in reasonable agreement with the available experimental data. Our conclusion is that cgDNA can serve as a highly efficient tool for studying structural variations in B-form DNA over a wide range of sequences.

Rapidly progressive cognitive impairment in a patient with high flow dural arteriovenous fistulas, cerebral sinus thrombosis and protein S deficiency.

Dural arteriovenous fistula (DAVF) may present with a variety of neurological symptoms, ranging from tinnitus to fatal hemorrhage. We report a case of rapidly progressive cognitive impairment due to cerebral venous engorgement that reversed after endovascular treatment in a patient with DAVF, cerebral sinus thrombosis and protein S deficiency. DAVF may be a cause of vascular cognitive impairment and should be considered particularly in cases with a rapidly progressive course because they are potentially treatable.

Malaria morbidity in Papua Indonesia, an area with multidrug resistant Plasmodium vivax and Plasmodium falciparum.

BACKGROUND: Multidrug resistance has emerged to both Plasmodium vivax and Plasmodium falciparum and yet the comparative epidemiology of these infections is poorly defined. METHODS: All laboratory-confirmed episodes of malaria in Timika, Papua, Indonesia, presenting to community primary care clinics and an inpatient facility were reviewed over a two-year period. In addition information was gathered from a house-to-house survey to quantify the prevalence of malaria and treatment-seeking behaviour of people with fever. RESULTS: Between January 2004 and December 2005, 99,158 laboratory-confirmed episodes of malaria were reported, of which 58% (57,938) were attributable to P. falciparum and 37% (36,471) to P. vivax. Malaria was most likely to be attributable to pure P. vivax in children under one year of age (55% 2,684/4,889). In the household survey, the prevalence of asexual parasitaemia was 7.5% (290/3,890) for P. falciparum and 6.4% (248/3,890) for P. vivax. The prevalence of P. falciparum infection peaked in young adults aged 15-25 years (9.8% 69/707), compared to P. vivax infection which peaked in children aged 1 to 4 years (9.5% 61/642). Overall 35% (1,813/5,255) of people questioned reported a febrile episode in the preceding month. Of the 60% of people who were estimated to have had malaria, only 39% would have been detected by the surveillance network. The overall incidence of malaria was therefore estimated as 876 per 1,000 per year (Range: 711-906). CONCLUSION: In this region of multidrug-resistant P. vivax and P. falciparum, both species are associated with substantial morbidity, but with significant differences in the age-related risk of infection.

Treatment of experimental renal osteodystrophy with pamidronate.

We evaluated the effects of the bisphosphonate pamidronate on bone histomorphometry, structure and strength in male rats with uninephrectomy or with chronic renal disease induced by 5/6 nephrectomy. In rats with chronic renal disease the plasma urea, phosphate and parathyroid hormone levels were significantly increased compared to rats with a uninephroctomy and none of these parameters was affected by pamidronate treatment. In the femoral midshaft, chronic renal disease reduced cortical bone mineral density and content. No difference was observed in the breaking load of the femoral midshaft. In the distal femur, a high-turnover renal osteodystrophy was found but pamidronate suppressed this bone turnover and increased bone mineral content. Treatment had no effect on chronic disease-induced augmentation of osteoid volume or fibroblast surface. These studies show that in this model of stage 3 renal disease, pamidronate increased mineral content in the femoral midshaft and distal metaphysis primarily by adding bone to endocortical and trabecular surfaces but did not reduce osteitis fibrosa.

Release of chlorhexidine digluconate and flexural properties of glass fibre reinforced provisional fixed partial denture polymer.

The objective of this study was to determine the flexural properties and the release of chlorhexidine digluconate (CHX) of CHX laced unidirectional E-glass fibre reinforced provisional fixed partial denture polymer. Bar shaped test specimens (3.3 x 10.0 x 65.0 mm) were fabricated from provisional fixed partial denture polymer (mixture of poly[ethylmethacrylate] powder and n-poly[butyl methacrylate] monomer liquid) with E-glass fibre reinforcements. Poly(methyl methacrylate) preimpregnated continuous unidirectional glass fibre reinforcement was laced with CHX. The glass fibre reinforcements were incorporated into the polymer and the polymerised to the form of test specimens. In addition test specimens without CHX in glass fibre reinforcement were made for comparison. Control specimens did not contain glass fibres in the test specimens. Flexural strength and modulus of test specimens (n = 6) was tested with three-point bending test after storing the specimens dry or in water (two weeks). Released CHX was determined with high performance liquid chromatography during 180 days water immersion. In dry conditions, the flexural strength and the modulus of the polymer was 43 MPa and 1.7 GPa, and with glass fibre reinforcement 96 MPa and 3.5 GPa. With the reinforcement laced with CHX, the strength was 92 MPa and the modulus was 3.2 GPa. The water storage of test specimens did not weaken the reinforced polymer. The majority of the CHX released from the glass fibre reinforced polymer during the first days of storage in water. Flexural properties of provisional fixed partial denture polymer were increased using glass fibre reinforcement. The fibre reinforcement that was laced with CHX resulted in similar reinforcing effect.

[A case of odontoma. Importance of an objective examination]. / Su un caso di odontoma. Importanza dell'esame obiettivo.

A case of odontoma which escaped attention at first objective examination and panoramic radiography makes it possible to stress the primary importance of inspection in dental practice.

Cisplatin and etoposide salvage therapy and resection of the residual tumor in pretreated germ cell testicular cancer.

Thirty-two consecutive patients with pretreated germinal testis cancer received three to four inductions of cisplatin and etoposide therapy (PE). Patients not pretreated, or only partially pretreated with bleomycin (B), also received this drug for a maximum of 12 doses. Sixteen patients underwent secondary surgery for the removal of residual masses. Twelve (37.5%) entered complete remission (CR) with chemotherapy alone, and an additional 9 cases (28%) were rendered tumor-free by surgery. The 21 disease-free patients (65.5%) received two further inductions and no maintenance. Toxicity was moderate, and 1 of the 16 patients who underwent surgery died postoperatively of pulmonary embolism. After a median follow-up period of 26 months (range, 9-60), 2 patients have died in CR and 15 (47%) are currently alive and have been continuously disease-free. The major determinant of tumor response was prior therapy. Eleven of 14 (78%) patients who were not pretreated with cisplatin achieved a continuous disease-free status versus only 4 of the 18 pretreated patients (22%, P less than 0.01). In this set of cases, complete responders to prior PVB therapy did better than incomplete responders treated for tumor progression. It can be concluded that normal-dose PE +/- B therapy, followed by surgical resection of the residual tumor, is a satisfactory salvage therapy in patients not pretreated with cisplatin and is also active in complete responders to prior PVB therapy.

Early resection of residual tumor during cisplatin, vinblastine, bleomycin combination chemotherapy in stage III and bulky stage II nonseminomatous testicular cancer.

Sixty consecutive patients with Stage III or bulky Stage II nonseminomatous germinal testis tumors were treated with cisplatin, vinblastine, bleomycin combination chemotherapy (PVB). One patient died of acute toxicity after the first course of therapy, 16 entered complete remission (CR) after two or three inductions, and 36 underwent surgery for removal of residual masses after the third cycle. No residual tumor was found in 16 cases, 10 had mature teratoma, and residual malignant tumor was completely resected in 8 of 10 patients. On the whole, 52 of 59 cases (88%) who completed the therapy entered CR, 34 (58%) with PVB and 18 (30%) with PVB and resection of the residual disease. The major beneficiaries of surgery were patients with bulky metastases (17 of 45, 38%) and those with primary teratocarcinoma (13 of 24, 54%). All of the patients who entered CR received two additional inductions and no maintenance. After a median follow-up period of greater than 3 years, 40 patients (68%) remain continuously disease-free, 1 died in CR, and 3 of the 11 who had relapse were salvaged. All of the 32 patients with lung deposits less than 5 cm and/or lymph node metastases less than 10 cm entered CR after the combined treatment modality, and 29 (91%) are alive disease-free. Also, 20 of 27 patients (74%) with far-advanced disease (lung and lymph node metastases larger than 5 and 10 cm, respectively, extrapulmonary disease) entered CR after PVB and surgery, but only 11 (41%) are continuously disease-free. Early resection of the residual tumor during PVB combination chemotherapy greatly increased the CR rate, but relapses were very frequent in patients with far-advanced disease.

Relapse pattern of pathologic stage I nonseminomatous germ cell tumors of the testis following orchidectomy and lymphadenectomy.

A retrospective analysis of patients with pathologic stage I nonseminomatous germinal testis tumors treated with orchidectomy and retroperitoneal lymphadenectomy was done in an attempt to define the relapse pattern and to eventually identify risk factors predisposing to tumor recurrence. Of 102 patients, 91 (89.2%) remain disease free with a median follow-up of greater than 5 years (range 3-10 years), and 11 (10.8%) suffered relapse 3-35 months after lymphadenectomy (median free interval 6 months). 9 of 11 patients developed primarily intrathoracic recurrences. The tumor was so rapidly progressing at relapse, that it was diagnosed when clinically advanced in 7 of 11 cases. Nevertheless, 8 of 11 patients were salvaged with effective available chemotherapy and resection of residual disease. Only scrotal violation showed a significant increased risk of tumor recurrence (5 of 24 cases, versus 6 of 78 who had inguinal orchidectomy, p less than 0.05). We recommend a very close follow-up for all patients with pathologically assessed stage I nonseminomatous germinal testis tumors during the first 3 years following orchidectomy and retroperitoneal lymphadenectomy. With early recognition of relapse, an approximately 100% cure rate will be achieved with effective available chemotherapy.

The antiemetic effect of methylprednisolone in patients treated with cis-platinum (CDDP) for advanced testicular germ cell tumors.

In cis-platinum treatment, nausea and vomiting are very serious side-effects and patients may be reluctant to accept or continue therapy. The purpose of this study is to verify the antiemetic effect of methylprednisolone in patients treated with cis-platinum in combination with other chemotherapeutic agents. Methylprednisolone in doses of 100 mg/m2 i.v. per 5 consecutive days was given to 33 patients receiving cis-platinum combination chemotherapies (134 cycles) at the Istituto Nazionale Tumori of Milan for advanced germ cell tumors of the testis. Seventy percent of cycles were partially or completely protected from vomiting. Only minor side-effects caused by methylprednisolone were observed. From this study it appears that methylprednisolone is an effective antiemetic drug in patients receiving cis-platinum combination chemotherapy.