Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort.

BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

The tale of an endemic shrimp's exceptional osmoregulation and the ancient Athalassic mangrove oasis.

The hyperarid mangrove in the Middle East is characterised by the absence of rivers or freshwater inputs and is one of the most extreme settings of this ecosystem on Earth. Endemic to Qatar's hyperarid mangroves, a Palaemon shrimp is uniquely confined to a sole mangrove site in the Arabian Gulf. Within these mangrove channels, we unveiled brine groundwater sources exceeding 70 ppt salinity, contrasting the local marine standard of 42 ppt. Concurrently, a mysid species typically linked to salt pans and groundwater coexists. Stable isotopic analysis implied the existence of a predator-prey dynamic between this mysid species and the studied shrimp. Then, investigating the endemic shrimp's adaptation to extreme salinity, we conducted osmolarity experiments and phylogenetic studies. Our findings demonstrate that this shrimp transitions from hypo- to hyper-osmoregulation, tolerating salinities from 18 to 68 ppt-an unprecedented osmoregulatory capacity among caridean shrimps. This speciation pattern likely arises from the species osmolarity adaptation, as suggested for other Palaemon congeners. Phylogenetic analysis of the studied Palaemon, along with the mangrove's geological history, suggests a profound evolutionary interplay between the ecosystem and the shrimp since the Eocene. This study proposes the hyperarid mangrove enclave as an Athalassic mangrove oasis-a distinctive, isolated ecosystem within the desert landscape.

Comparison of the distraction index and Norberg angle with radiographic grading of canine hip dysplasia.

The Orthopedic Foundation for Animals (OFA) radiographic grading system stands as a well-established benchmark for categorizing hip dysplasia in canines. Although more objective techniques to quantify early hip laxity in young dogs, such as the Norberg angle (NA) and distraction index (DI), have been documented, there is a scarcity of published studies that directly compare these radiographic measures. The primary objectives of this prospective, analytical study were to assess and compare the NA and DI measures with OFA grades within a cohort of dogs. Thirty dogs (57 hip joints) were evaluated, with a mean age of 5.4 ± 2.9 years and a mean body weight of 34.3 ± 7.1 kg. The discriminative power of hip dysplasia for DI and NA used OFA as a reference were compared by multivariate discriminant analysis test. Using the DI (≤0.3) 12 joints were classified as normal, using NA (≥105°) 24 joints and using OFA (≤3) 29. When comparing the discriminant power of NA with OFA resulting similar (P = .8324) with correct classifications of 81% using cross validation, however, the discriminant power of dysplasia of the DI resulted significantly greater (P = .0034) than OFA with correct classifications of only 59% using cross-validation, consequently it was possible determined that of 29 patients with OFA ≤ 3, 20 had DI > 0.3. These findings demonstrated that phenotypic healthy dogs according to OFA grading can present passive hip joint laxity, as demonstrated by radiographic evaluation with distraction. Furthermore, DI can contribute to the screening of CHD when evaluated in conjunction with OFA grading.

Early Surgical Management of Medial Patellar Luxation in Juvenile Dogs.

The aim of this study was to analyse a series of five cases of early surgical treatment in juvenile canine patients with high-grade medial patellar luxation. Canine patients, with immature skeleton, affected by grade III or IV medial patellar luxation and treated by multimodal surgical techniques were selected. Five dogs of different breeds, mean age 7.2 ± 3.0 months, met the inclusion criteria. Simultaneous distal femoral varus and external tibial torsion were identified in three of the five cases, whereas in the others, femoral varus with associated tibial valgus and isolated external tibial torsion were observed. Four of the five patients were treated surgically with closing wedge osteotomy of the distal femur, and three of them underwent tibial tuberosity transposition simultaneously. Only two animals required trochleoplasty. Mean time to beginning of weight bearing was 9.8 ± 5.5 days, whereas time to bone healing was 55 ± 24 days. Bone realignment of the extensor apparatus and return to limb support were achieved in all cases. Postoperative reintervention was needed in one patient; however, it was not linked to the initial surgery. Patients were followed up to 1 year postoperatively, with maintenance of extensor alignment and no late complications. The early surgical approach has been shown to be effective in the definitive treatment of juvenile dogs affected by high-grade medial patellar luxation.

Expanding ocean protection and peace: a window for science diplomacy in the Gulf.

The ecological state of the Persian or Arabian Gulf (hereafter 'Gulf') is in sharp decline. Calls for comprehensive ecosystem-based management approaches and transboundary conservation have gone largely unanswered, despite mounting marine threats made worse by climate change. The region's long-standing political tensions add additional complexity, especially now as some Gulf countries will soon adopt ambitious goals to protect their marine environments as part of new global environmental commitments. The recent interest in global commitments comes at a time when diplomatic relations among all Gulf countries are improving. There is a window of opportunity for Gulf countries to meet global marine biodiversity conservation commitments, but only if scientists engage in peer-to-peer diplomacy to build trust, share knowledge and strategize marine conservation options across boundaries. The Gulf region needs more ocean diplomacy and coordination; just as critically, it needs actors at its science-policy interface to find better ways of adapting cooperative models to fit its unique marine environment, political context and culture. We propose a practical agenda for scientist-led diplomacy in the short term and lines of research from which to draw (e.g. co-production, knowledge exchange) to better design future science diplomacy practices and processes suited to the Gulf's setting.

Effects of Human Observer Presence on Pain Assessment Using Facial Expressions in Rabbits.

The goal of this study was to evaluate the effect of a human observer on Rabbit Grimace Scale (RbtGS) scores. The study scored video footage taken of 28 rabbits before and after orthopedic surgery, as follows: 24 h before surgery ( baseline), 1 h after surgery ( pain), 3 h after analgesia administration ( analgesia), and 24 h after surgery ( 24h) in the presence and absence of an observer. Videos were assessed twice in random order by 3 evaluators who were blind to the collection time and the presence or absence of an observer. Responses to pain and analgesia were evaluated by comparing the 4 time points using the Friedman test, followed by the Dunn test. The influence of the presence or absence of the observer at each time point was evaluated using the Wilcoxon test. Intra- and interrater reliabilities were estimated using the intraclass correlation coefficient. The scale was responsive to pain, as the scores increased after surgery and had decreased by 24 h after surgery. The presence of the observer reduced significantly the RbtGS scores (median and range) at pain (present, 0.75, 0 to 1.75; absent, 1, 0 to 2) and increased the scores at baseline (present, 0.2, 0 to 2; absent, 0, 0 to 2) and 24h after surgery (present, 0.33, 0 to 1.75; absent, 0.2, 0 to 1.5). The intrarater reliability was good (0.69) to very good (0.82) and interrater reliability was moderate (0.49) to good (0.67). Thus, the RbtGS appeared to detect pain when scored from video footage of rabbits before and after orthopedic surgery. In the presence of the observer, the pain scores were underestimated at the time considered to be associated with the greatest pain and overestimated at the times of little or no pain.

Oxygen transfer and gas holdup in airlift bioreactors assembled with helical flow promoters.

Bioreactors can perform biochemical conversions mediated by biocatalysts, such as enzymes, animal cells, plants, and microorganisms. Among several existing models, airlift bioreactors are devices with the low shear environment and good mass transfer with low energy consumption, employed in several biochemical processes. The fluid flow is enabled through air injection by the sparger located at the bioreactor base. Despite its simple geometry compared with the conventional bioreactors, airlift performance can be optimized via geometrical modifications. Therefore, the objective of this work was to evaluate the effects of the addition of helical flow promoters, positioned in the riser and/or downcomer regions of an airlift of concentric tubes measuring the volumetric oxygen coefficient (kLa) and gas holdup. The results obtained by varying the gas flow rate from 1.0 to 4.0 vvm allowed the system evaluation of oxygen transfer and gas holdup. The inclusion of helical flow promoters increased the kLa, reaching up to 23% in oxygen transfer compared to tests without helicoids and up to 14% increase in the gas holdup. The inclusion of helical flow promotors was beneficial for all gas flow rates. Thus, including these flow promoters is an effective strategy to increase the oxygen transfer rate for bioprocess optimization.

Preliminary study on a novel dedicated plate for iliac fractures in dogs.

INTRODUCTION: The aim of this study was to describe and evaluate a novel plate designed specifically for the canine ilium using finite element methods. The cranial portion of the plate had an elliptical shape and contained nine screw holes. The caudal portion of the plate was triangular with three screw holes. Four and three screws were used at the cranial (screw 1 to 4) and caudal (screw 5 to 7) segment of the plate. Finite element models of the plate and canine pelvis were created. A load of 300 N was applied on the femur-hip joint contact area. Values of Von Mises Stress on the plate, screws and the maximum and minimum main stresses in the bone were used to capture the mechanical factors in this study. RESULTS: The novel implant had a plate stress of 51.9 megapascals (MPa) with higher stress in the dorsal part of the plate. Screws 2 and 4 showed similar stress values of 17.3 MPa. Screws 1 and 3 were the most loaded (51.9 MPa and 75 MPa, respectively). Screws 5, 6, and 7 showed similar dissipation and stress values (21.55 MPa). There was traction force in the dorsal region of the pubis and compression in the ventral part, with dissipation and values of 15.4 MPa and 23.9 MPa, respectively, acquiring balance between them. CONCLUSION: The novel plate is potentially applicable and specifically suitable for iliac fractures in dogs. The screws distribution modeled proved itself strategical since the simulated stresses were evenly distributed throughout the implant construct.

Predictors of germline status for hereditary melanoma: 5 years of multi-gene panel testing within the Italian Melanoma Intergroup.

BACKGROUND: The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date. MATERIALS AND METHODS: From 25 Italian centers, we recruited 1044 family members and germline sequenced 940 cutaneous melanoma index cases through a shared gene panel, which included the following genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, MITF and ATM. We assessed detection rate according to familial status, region of origin, number of melanomas and presence and type of non-melanoma tumors. RESULTS: The overall detection rate was 9.47% (5.53% analyzing CDKN2A alone), ranging from 5.14% in sporadic multiple melanoma cases (spoMPM) with two cutaneous melanomas to 13.9% in familial cases with at least three affected members. Three or more cutaneous melanomas in spoMPM cases, pancreatic cancer and region of origin predicted germline status [odds ratio (OR) = 3.23, 3.15, 2.43, P < 0.05]. Conversely, age > 60 years was a negative independent predictor (OR = 0.13, P = 0.008), and was the age category with the lowest detection rate, especially for CDKN2A. Detection rate was 19% when cutaneous melanoma and pancreatic cancer clustered together. CONCLUSIONS: Gene panel doubled the detection rate given by CDKN2A alone. National genetic testing criteria may need a revision, especially regarding age cut-off (60) in the absence of strong family history, pancreatic cancer and/or a high number of cutaneous melanomas.

2,5-Diketopiperazines via Intramolecular N-Alkylation of Ugi Adducts: A Contribution to the Synthesis, Density Functional Theory Study, X-ray Characterization, and Potential Herbicide Application.

To investigate the herbicidal potential of 2,5-diketopiperazines (2,5-DKPs), we applied a known protocol to produce a series of 2,5-DKPs through intramolecular N-alkylation of Ugi adducts. However, the method was not successful for the cyclization of adducts presenting aromatic rings with some substituents at the ortho position. Results from DFT calculations showed that the presence of voluminous groups at the ortho position of a benzene ring results in destabilization of the transition structure. Lower activation enthalpies for the SN2-type cyclization of Ugi adducts were obtained when bromine, instead of a chlorine anion, is the leaving group, indicating that the activation enthalpy for the cyclization step controls the formation of the 2,5-DKP. Some Ugi adducts and 2,5-DKPs formed crystals with suitable qualities for single-crystal X-ray diffraction data collection. Phytotoxic damage of some 2,5-DKPs on leaves of the weed Euphorbia heterophylla did not differ from those caused by the commercial herbicide diquat.

Modified tibial plateau levelling osteotomy to treat lateral patellar luxation and cranial cruciate ligament deficiency in a dog.

The use of modified tibial plateau leveling osteotomy adapted for correction of the lateral patellar dislocation was effective, allowing simultaneous treatment of lateral patellar luxation and cranial cruciate ligament deficiency.

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

Proteolytic activity of Triatoma infestans saliva associated with PAR-2 activation and vasodilation.

BACKGROUND: Triatoma infestans (Hemiptera: Reduviidae) is a hematophagous insect and the main vector of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae). In the present study, the authors investigated whether a serine protease activity from the saliva of T. infestans has a role in vasomotor modulation, and in the insect-blood feeding by cleaving and activating protease-activated receptors (PARs). METHODS: T. infestans saliva was chromatographed as previously reported for purification of triapsin, a serine protease. The cleavage activity of triapsin on PAR peptides was investigated based on FRET technology. Mass spectrometry was used to analyze the sites of PAR-2 peptide cleaved by triapsin. NO measurements were performed using the DAN assay (2,3-diaminonapthalene). The vasorelaxant activity of triapsin was measured in vessels with or without functional endothelium pre-contracted with phenylephrine (3 µM). Intravital microscopy was used to assess the effect of triapsin on mouse skin microcirculation. RESULTS: Triapsin was able to induce hydrolysis of PAR peptides and showed a higher preference for cleavage of the PAR-2 peptide. Analysis by mass spectrometry confirmed a single cleavage site, which corresponds to the activation site of the PAR-2 receptor. Triapsin induced dose-dependent NO release in cultured human umbilical vein endothelial cells (HUVECs), reaching a maximum effect at 17.58 nM. Triapsin purified by gel-filtration chromatography (10-16 to 10-9 M) was applied cumulatively to mouse mesenteric artery rings and showed a potent endothelium-dependent vasodilator effect (EC30 = 10-12 M). Nitric oxide seems to be partially responsible for this vasodilator effect because L-NAME (L-NG-nitroarginine methyl ester 300 µM), a nitric oxide synthetase inhibitor, did not abrogate the vasodilation activated by triapsin. Anti-PAR-2 antibody completely inhibited vasodilation observed in the presence of triapsin activity. Triapsin activity also induced an increase in the mouse ear venular diameter. CONCLUSION: Data from this study suggest a plausible association between triapsin activity mediated PAR-2 activation and vasodilation caused by T. infestans saliva.

Whole genome sequencing of marine organisms by Oxford Nanopore Technologies: Assessment and optimization of HMW-DNA extraction protocols.

Marine habitats are Earth's largest aquatic ecosystems, yet little is known about marine organism's genomes. Molecular studies can unravel their genetics print, thus shedding light on specie's adaptation and speciation with precise authentication. However, extracting high molecular weight DNA from marine organisms and subsequent DNA library preparation for whole genome sequencing is challenging. The challenges can be explained by excessive metabolites secretion that co-precipitates with DNA and barricades their sequencing. In this work, we sought to resolve this issue by describing an optimized isolation method and comparing its performance with the most commonly reported protocols or commercial kits: SDS/phenol-chloroform method, Qiagen Genomic Tips kit, Qiagen DNeasy Plant mini kit, a modified protocol of Qiagen DNeasy Plant kit, Qiagen DNeasy Blood and Tissue kit, and Qiagen Qiamp DNA Stool mini kit. Our method proved to work significantly better for different marine species regardless of their shape, consistency, and sample preservation, improving Oxford Nanopore Technologies sequencing yield by 39 folds for Spirobranchus sp. and enabling generation of almost 10 GB data per flow cell/run for Chrysaora sp. and Palaemon sp. samples.

Proteolytic activity of Triatoma infestans saliva associated with PAR-2 activation and vasodilation

Triatoma infestans (Hemiptera: Reduviidae) is a hematophagous insect and the main vector of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae). In the present study, the authors investigated whether a serine protease activity from the saliva of T. infestans has a role in vasomotor modulation, and in the insect-blood feeding by cleaving and activating protease-activated receptors (PARs). Methods T. infestans saliva was chromatographed as previously reported for purification of triapsin, a serine protease. The cleavage activity of triapsin on PAR peptides was investigated based on FRET technology. Mass spectrometry was used to analyze the sites of PAR-2 peptide cleaved by triapsin. NO measurements were performed using the DAN assay (2,3-diaminonapthalene). The vasorelaxant activity of triapsin was measured in vessels with or without functional endothelium pre-contracted with phenylephrine (3 µM). Intravital microscopy was used to assess the effect of triapsin on mouse skin microcirculation. Results Triapsin was able to induce hydrolysis of PAR peptides and showed a higher preference for cleavage of the PAR-2 peptide. Analysis by mass spectrometry confirmed a single cleavage site, which corresponds to the activation site of the PAR-2 receptor. Triapsin induced dose-dependent NO release in cultured human umbilical vein endothelial cells (HUVECs), reaching a maximum effect at 17.58 nM. Triapsin purified by gel-filtration chromatography (10-16 to 10-9 M) was applied cumulatively to mouse mesenteric artery rings and showed a potent endothelium-dependent vasodilator effect (EC30 = 10-12 M). Nitric oxide seems to be partially responsible for this vasodilator effect because L-NAME (L-NG-nitroarginine methyl ester 300 µM), a nitric oxide synthetase inhibitor, did not abrogate the vasodilation activated by triapsin. Anti-PAR-2 antibody completely inhibited vasodilation observed in the presence of triapsin activity. Triapsin activity also induced an increase in the mouse ear venular diameter. Conclusion Data from this study suggest a plausible association between triapsin activity mediated PAR-2 activation and vasodilation caused by T. infestans saliva.(AU)

Effects of lumbar myelography on subarachnoid pressure and cardiorespiratory parameters in healthy sheep

ABSTRACT: The purpose of this study was to evaluate the effects of lumbar myelography on subarachnoid pressure, cardiorespiratory parameters and pressure-volume index in sheep. Eight sheep were evaluated. The animals were submitted to puncture of the cisterna magna for monitoring of subarachnoid pressure (SaP). Lumbar myelography was performed through applying Iohexol (0.4mL/kg). ToC, PAS, PAD, MAP, InspISO, FeISO, SaP and CPP were recorded immediately after anesthetic stabilization (M0), during lumbar puncture (M1), and two, four and six minutes after contrast application (M2, M3 and M4, respectively). Blood pressure initially increased, then decreased, returning to basal level, similarly observed for InspISo and FeISo. The SaP rose initially thereafter remaining stable. Despite of the effect on subarachnoid pressure, lumbar myelography can be considered safe in sheep.

RESUMO: O objetivo foi avaliar os efeitos da mielografia lombar na pressão subaracnóidea, parâmetros cardiorrespiratórios e índice pressão-volume em ovinos. Oito ovelhas foram avaliadas. Os animais foram submetidos à punção da cisterna magna para monitoramento da pressão subaracnoidea (SaP). A mielografia lombar foi realizada com a aplicação de Iohexol (0,4mL/kg). Os momentos estudados foram: imediatamente após a estabilização anestésica (M0), durante a punção lombar (M1), dois, quatro e seis minutos após a aplicação do contraste (M2, M3 e M4, respectivamente), para avaliar as seguintes variáveis: ToC, PAS, PAD, MAP, InspISO, FeISO, Sap e CPP. A pressão arterial aumentou inicialmente, depois diminuiu, retornando aos valores iniciais, padrão também observado para o InspISo e o FeISo. O SaP subiu inicialmente, posteriormente, permanecendo estável. A mielografia lombar, apesar de influenciar a pressão subaracnoidea, pode ser considerada segura em ovinos.

Effects of lumbar myelography on subarachnoid pressure and cardiorespiratory parameters in healthy sheep / Efeitos da mielografia lombar na pressão subaracnoidea e nos parâmetros cardiorrespiratórios em ovelhas saudáveis

The purpose of this study was to evaluate the effects of lumbar myelography on subarachnoid pressure, cardiorespiratory parameters and pressure-volume index in sheep. Eight sheep were evaluated. The animals were submitted to puncture of the cisterna magna for monitoring of subarachnoid pressure (SaP). Lumbar myelography was performed through applying Iohexol (0.4mL/kg). ToC, PAS, PAD, MAP, InspISO, FeISO, SaP and CPP were recorded immediately after anesthetic stabilization (M0), during lumbar puncture (M1), and two, four and six minutes after contrast application (M2, M3 and M4, respectively). Blood pressure initially increased, then decreased, returning to basal level, similarly observed for InspISo and FeISo. The SaP rose initially thereafter remaining stable. Despite of the effect on subarachnoid pressure, lumbar myelography can be considered safe in sheep.(AU)

O objetivo foi avaliar os efeitos da mielografia lombar na pressão subaracnóidea, parâmetros cardiorrespiratórios e índice pressão-volume em ovinos. Oito ovelhas foram avaliadas. Os animais foram submetidos à punção da cisterna magna para monitoramento da pressão subaracnoidea (SaP). A mielografia lombar foi realizada com a aplicação de Iohexol (0,4mL/kg). Os momentos estudados foram: imediatamente após a estabilização anestésica (M0), durante a punção lombar (M1), dois, quatro e seis minutos após a aplicação do contraste (M2, M3 e M4, respectivamente), para avaliar as seguintes variáveis: ToC, PAS, PAD, MAP, InspISO, FeISO, Sap e CPP. A pressão arterial aumentou inicialmente, depois diminuiu, retornando aos valores iniciais, padrão também observado para o InspISo e o FeISo. O SaP subiu inicialmente, posteriormente, permanecendo estável. A mielografia lombar, apesar de influenciar a pressão subaracnoidea, pode ser considerada segura em ovinos.(AU)

Bioactive Aliphatic Sulfates from Marine Invertebrates.

The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene aliphatic sulfates are considerably rarer with examples being reported from a diverse array of organisms including echinoderms, sponges and ascidians. While no ecological roles for these metabolites have been proposed, they do exhibit a diverse array of biological activities including thrombin inhibition; the ability to induce metamorphosis in larvae; antiproliferative, antibacterial and antifungal properties; and metalloproteinase inhibition. Of particular interest and an avenue for future development is the finding of antifouling properties with low or nontoxic effects to the environment. This review focuses on alkyl sulfates and related sulfamates, their structures and biological activities. Spectroscopic and spectrometric techniques that can be used to recognize the presence of sulfate groups are also discussed, data for which will enhance the ability of researchers to recognize this class of chemically- and biologically-interesting marine natural products.

Lyophilized and gamma-sterilized allogeneic bone implant used as a spacer for advancement of a modified tibial tuberosity in the treatment of cranial cruciate ligament disease in dogs.

The objective of this study was to evaluate the use of a lyophilized and gamma-sterilized allogeneic freeze-dried bone wedge as a spacer for advancement of a modified tibial tuberosity (mTTA) in 16 knees that were clinically diagnosed with cranial cruciate ligament disease. Patients underwent radiography before the surgical procedure as well as immediately after surgery and at 30, 60, 90 and 120 days post-surgery, and their locomotion was evaluated at the same time points except for the immediate postoperative period. The surgical wounds were evaluated for signs of infection and rejection of the bone implant. Locomotion was graded on a scale of 0-5, with 0 indicating no limping and 5 indicating limb functional impotence. The "tibial-tibial bone-tibial implant" interfaces were evaluated radiographically, and each interface was assigned scores of 0-3, with 0 indicating no contact between the implant and adjacent bone and 3 indicating a bone bridge throughout the interface. The patients showed good clinical and radiographic recovery. The lyophilized bone spacer allowed for easy storage and transport and rapid and satisfactory execution of mTTA while showing resistance to drilling and fixation with screws in 87.5% of cases and a mean surgical time of 45.9 minutes. No immunogenic reactions were observed in 93.7% of the cases. One patient presented infection of the surgical focus, which showed remission after antimicrobial therapy. All patients showed functional recovery of the operated limb, with the number of clinically healthy patients being higher than those with claudication at 120 days (p ≤ 0.05). In all patients, it was possible to verify the incorporation of the bone implant into the tibia. Bone union occurred progressively, and the degrees of bone union observed on radiographs at postoperative days 60, 90, and 120 were significantly greater (p < 0.05) than those observed in the immediate postoperative period and at 30 days.

Accuracy in Determining Canal Flare Index Using Different Radiographical Positions for Imaging Canine Femurs.

OBJECTIVE: The aim of this study was to compare in vitro accuracy of femoral measurements obtained from different radiographical positions with actual femoral anatomical dimensions in dogs. MATERIALS AND METHODS: Craniocaudal projections of the femur in ventrodorsal position, standard craniocaudal radiographical (SR) and craniocaudal radiography with horizontal radiographical beam (HR), in addition to anatomical macroscopic measurements (A), were obtained from 45 femurs from 23 canine cadavers, for calculation of the canal flare index (CFI). The differences between the radiographical positions and 95% limits of agreement (LOA) between the CFI-SR, CFI-HR and CFI-A were evaluated by the Bland-Altman method. RESULTS: The standard craniocaudal radiograph provided an approximate dimension of the proximal femoral morphology (mean difference: 0.121 ± 0.391) with a different CFI value (p = 0.0341) from CFI-A. The craniocaudal radiograph taken using a horizontal beam provided greater accuracy (mean difference: 0.087 ± 0.42) in our study. CLINICAL SIGNIFICANCE: The craniocaudal projection using a horizontal radiographical beam was more accurate than the standard craniocaudal projection for measurement of the true anatomical dimensions of the canine femur, minimizing the influence of the technique on the CFI values.