VAAFT for complex anal fistula: a useful tool, however, cure is unlikely.

BACKGROUND: Therapeutic options for complex anal fistula (CAF) are limited. Video-assisted anal fistula treatment (VAAFT) allows examination of these anatomically complex fistulae from within. The aim of the present study was to evaluate outcomes of VAAFT for a series of CAF. METHODS: A retrospective study was conducted on consecutive patients at a single centre with complex anal cryptoglandular and Crohn's fistulae managed with VAAFT from June 2016 to June 2019. CAF was diagnosed as high intersphincteric/transsphincteric tract, multiple/secondary tracts, horseshoe or anovaginal fistulae. Patients were treated with 'therapeutic intent' if the internal opening was closed at the time of ablation and 'diagnostic/staged/palliative' VAAFT if there was no ablation/partial treatment/ablation-only, respectively. Symptom improvement was a reduction in reported pain, discharge, or pad use. RESULTS: Eighty-four patients (73 cryptoglandular, 11 Crohn's, M:F 2.5:1, median age 43 [22-77] years), underwent 105 VAAFT procedures. Twenty patients had > 1 VAAFT. Median follow-up was 8 (1-46) months. 40 (48%) had multiple or secondary tracts; an additional 16 (19%) had horseshoe and 3 (4%) anovaginal fistulae. Of the 84 patients, 19 [16/73 (22%) cryptoglandular and 3/11 (27%) Crohn's fistulae] healed. 34 (40%) unhealed reported improved symptoms; 23 (27%) no improvement; and 6 (7%) were worse. Sixteen (19%) had CAF > 5 years of whom none healed, albeit 50% reported symptom improvement. Five patients (6%) developed faecal incontinence: 2 temporary, 1 to flatus only and 1 to liquid and 1 to solid, all managed conservatively. CONCLUSIONS: VAAFT is a useful minimally invasive procedure for complex fistula with no other minimally invasive options. Complete healing is rare, and, although symptoms can be improved in a number of cases, there is a small risk of incontinence.

Brachial-ankle pulse wave velocity with a custom device. / Velocidad de onda de pulso brazo-tobillo con un dispositivo propio.

BACKGROUND AND OBJECTIVES: The brachial-ankle pulse wave velocity (baPWV) is one of the most widely used arterial stiffness variables for assessing vascular risk. The abiPWV is a device that calculates various PWVs and the blood pressure ankle-brachial index (ABI). The device can also determine baPWV. The aim of this study was to calculate the baPWV with abiPWV, validate it with a reference device (VaSera) and study its clinical usefulness. PATIENTS AND METHODS: We studied 113 patients (mean age, 53±12years), 59 (52%) of whom were women, and 10 (8.8%) of whom had a previous cardiovascular event. The participants were classified according to cardiovascular risk factors (CRFs) into groupI (none), groupII (1 or 2 CRFs) and groupIII (3 or more CRFs). The patients with a previous cardiovascular event were included in groupIII. All participants had their baPWV measured with abiPWV and VaSera. RESULTS: The baPWV correlation between the 2 devices was r=0.93 (P<.001), and the percentage error calculated with the Bland-Altman analysis was 4.5%. The baPWV measured with abiPWV (in m/s) was as follows: groupI, 10.5±1.6; groupII, 13.8±2.9 (P<.001 when compared with groupI); and groupIII, 14.1±2.7 (P<.001 when compared with groupI). There were no differences between groupsII and III. The results with VaSera were comparable to those of abiPWV. CONCLUSIONS: Measuring baPWV with the abiPWV is safe and has a similar clinical utility to that of VaSera. Incorporating this function into the options of abiPWV makes it a complete device for assessing arterial stiffness.

Assessment of metal and metalloid contamination in soils trough compositional data: the old Mortórios uranium mine area, central Portugal.

Soils from the old Mortórios uranium mine area were studied to look for contamination, as they are close to two villages, up to 3 km away, and used for agriculture. They are mainly contaminated in U and As and constitute an ecological threat. This study attempts to outline the degree to which soils have been affected by the old mining activities through the computation of significant hot clusters, Traditional geostatistical approaches commonly use raw data (concentrations) accepting that the analyzed elements represent the soil's entirety. However, in geochemical studies these elements are just a fraction of the total soil composition. Thus, considering compositional data is pivotal. The spatial characterization, considering raw and compositional data together, allowed a broad discussion about not only the concentrations' spatial distribution, but also a better understanding on the possibility of trends of "relative enrichment" and, furthermore an insight in U and As fate. The highest proportions (compositional data) on U (up to 33%), As (up to 35%) and Th (up to 13%) are reached in the south-southeast segment. However, the highest concentrations (raw data) occur in north and northwest of the studied area, pointing out to a "relative enrichment" toward the south-southeast zone. The Mondego Sul area is mainly contaminated in U and As, but also in Co, Cu, Pb and Sb. The Mortórios area is less contaminated than the Mondego Sul area.

Functional polymorphisms of interleukin-18 gene and risk of breast cancer in a Brazilian population.

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. In this case-control study, we tested whether IL-18 promoter polymorphism contributes to breast cancer susceptibility in Brazilian patients. The two groups studied were 154 patients with breast cancer and 118 healthy individuals. The frequency of IL-18 promoter single nucleotide polymorphisms (SNPs) at positions -607 (C/A) (rs1946518) and -137 (G/C) (rs187238) was determined by polymerase chain reaction analyses. The polymorphisms genotyped in this study showed a significant association with breast cancer under different genetic models. Both SNPs showed a positive association. For the IL18-607 polymorphism the best model was the codominant genetic model [CC vs AA, P = 0.004, odds ratio (OR) = 2.782, 95% confidence interval (CI) 1.385-5.589]. For IL18-137 statistical significance was found using the recessive genetic model (P = 0.008, OR = 3.896, 95% CI 1.427-10.639). The association between the haplotypes of the IL18 gene and breast cancer was further confirmed. Our results suggest that IL18-607 and IL18-137 polymorphism contributes to increase the breast cancer risk. To our knowledge, this is the first report regarding Brazilian breast cancer patients and IL18 promoter polymorphisms.

Anaesthetic management of tetraplegic pregnant patients during child delivery: A systematic review.

BACKGROUND: Pregnancy in spinal cord injured patients has specific issues that must be carefully addressed. However, guidelines for their management are scarce. METHODS: A systematic review of the literature regarding the anaesthetic management during delivery of pregnant patients with cervical spinal cord injury was performed on the electronic databases of PubMed (Medline) and Cochrane. RESULTS: Twenty-two papers were included. A higher incidence of preterm birth and caesarean delivery were seen. Anaesthetic management was diverse, although most pregnant patients received epidural analgesia. Autonomic dysreflexia symptoms were present in 51% of pregnancies. CONCLUSION: Timely management of these patients could possibly reduce caesarean and preterm delivery rates, avoid or minimize common complications, as well as reduce costs. An early reference to anaesthesiology consultation and a multidisciplinary approach is recommended.

The ultimate technique for posterior rib fractures: the parascapular sub-iliocostalis plane block - A series of cases.

We report retrospectively a series of four cases involving the successful use of the recently described parascapular sub-iliocostalis plane block (PSIP), for lateral-posterior rib fractures. The efficacy of the PSIP block may potentially depend on different mechanisms of action: (1) direct action in the fracture site by craniocaudal myofascial spread underneath the erector spinae muscle (ESM); (2) spread to deep layers through tissue disruption caused by trauma, to reach the proximal intercostal nerves; (3) medial spread below the ESM, to reach the posterior spinal nerves; and (4) lateral spread in the sub-serratus (SS) plane to reach the lateral cutaneous branches of the intercostal nerves; while avoiding significant negative hemodynamic effects and other possible complications associated to other techniques leading that the PSIP may be considered an alternative in some clinical scenarios to the Erector Spinae Plane block or the Paravertebral block.

Water deficit and salt stress diagnosis through LED induced chlorophyll fluorescence analysis in Jatropha curcas L.

LED induced chlorophyll fluorescence analysis is employed to investigate the effect of water deficit and salt stress upon the growth process of Jatropha curcas L.. Red(Fr) and far-red(FFr) chlorophyll fluorescence around 685 nm and 735 nm, respectively, were observed and examined as a function of the stress intensity(salt concentration and water deficit). The fluorescence ratio Fr/FFr which is a valuable nondestructive and nonintrusive indicator of the chlorophyll content of leaves was exploited to monitor the jatropha plants under stress. The data indicated that salinity plays a minor role in the chlorophyll concentration of leaves for NaCl concentrations in the 25 to 200 mM range. The fluorescence ratio also permitted the detection of damage caused by water deficit in the early stages of the plants growing process. A significant variation of the Fr/FFr ratio was observed in the first 10 days of the experiment, and before signs of visual stress became apparent. The results suggest that the Fr/FFr ratio is an early-warning indicator of water deficit stress.

Trypanosoma cruzi modulates lipid metabolism and highjacks phospholipids from the midgut of Rhodnius prolixus.

Chagas disease is potentially life-threatening and caused by the protozoan parasite Trypanosoma cruzi. The parasite cannot synthesize some lipids and depends on the uptake of these lipids from its vertebrate and invertebrate hosts. To achieve this, T. cruzi may need to modify the physiology of the insect host for its own benefit. In this study, we investigated the interaction of T. cruzi (Y strain) with its insect vector Rhodnius prolixus and how it manipulates the vector lipid metabolism. We observed a physiological change in lipid flux in of infected insects. In the fat body of infected insects, triacylglycerol levels decreased by 80.6% and lipid storage droplet-1(LSD-1) mRNA levels were lower, when compared to controls. Lipid sequestration by infected midguts led to increased levels of 5' AMP-activated protein kinase (AMPK) phosphorylation and activation in the fat body, inhibiting the synthesis of fatty acids and stimulating their oxidation. This led to reduced lipid levels in the fat body of infected insets, despite the fact that T. cruzi does not colonize this tissue. There was a 3-fold increase, in lipid uptake and synthesis in the midgut of infected insects. Finally, our results suggest that the parasite modifies the lipid flux and metabolism of its vector R. prolixus through the increase in lipid delivery from the fat body to midgut that are then scavenge by T cruzi.

Treatment of Symptomatic Functional Atrioventricular Block by Cardioneuroablation as an Alternative to Pacemaker Implantation.

A woman with recurrent presyncope caused by a functional atrioventricular (AV) block after meals, with limiting symptoms, underwent cardioneuroablation and AV node vagal denervation without pacemaker implantation. Normal AV conduction was recovered with complete abolishment of symptoms. (Level of Difficulty: Advanced.).

Technical note: Validation of candidate reference genes for normalization of quantitative PCR in bovine mammary epithelial cells responding to inflammatory stimuli.

Mammary epithelial cells (MEC) participate in the first line of defense of the mammary gland to invading pathogens. In vitro culture of MEC is widely used as a model to study the capacity of these cells to sense and respond to mastitis-causing bacteria. Analysis of gene expression by quantitative PCR (qPCR) following exposure to bacteria or bacterial constituents is a powerful tool to assess responses of MEC to pathogens. Although internal standards such as reference genes are required for qPCR to yield valid data, the validation of proper genes to quantify mRNA transcripts in MEC exposed to pro-inflammatory stimuli has never been reported. In this study, 10 commonly used reference genes belonging to different functional classes (ACTB, ATP5B, EIF2B2, GAPDH, PPIA, SDHA, SUZ12, UXT, YWHAZ, and 18s rRNA) were analyzed by qPCR to determine the most stable in bovine MEC unstimulated and stimulated with mastitis pathogens (Staphylococcus aureus or Escherichia coli), microbial agonists of the innate immune system (lipoteichoic acid and muramyl dipeptide, or lipopolysaccharide), or proinflammatory cytokines (IL-17A and tumor necrosis factor-α). An M value was used as a measure of gene stability as determined using the geNorm application. This study demonstrated that the expression of the 10 reference genes was stable under the different experimental conditions. These data will be useful for bovine mastitis research in selecting reference genes and validating reverse transcription-qPCR data.

Brachial-ankle pulse wave velocity with a custom device.

BACKGROUND AND OBJECTIVES: The brachial-ankle pulse wave velocity (baPWV) is one of the most widely used arterial stiffness variables for assessing vascular risk. The abiPWV is a device that calculates various PWVs and the blood pressure ankle-brachial index (ABI). The device can also determine baPWV. The aim of this study was to calculate the baPWV with abiPWV, validate it with a reference device (VaSera) and study its clinical usefulness. PATIENTS AND METHODS: We studied 113 patients (mean age, 53 ±â€¯12 years), 59 (52%) of whom were women, and 10 (8.8%) of whom had a previous cardiovascular event. The participants were classified according to cardiovascular risk factors (CRFs) into group I (none), group II (1 or 2 CRFs) and group III (3 or more CRFs). The patients with a previous cardiovascular event were included in group III. All participants had their baPWV measured with abiPWV and VaSera. RESULTS: The baPWV correlation between the 2 devices was r = 0.93 (p < .001), and the percentage error calculated with the Bland-Altman analysis was 4.5%. The baPWV measured with abiPWV (in m/s) was as follows: group I, 10.5 ±â€¯1.6; group II, 13.8 ±â€¯2.9 (p < .001 when compared with group I); and group III, 14.1 ±â€¯2.7 (p < .001 when compared with group I). There were no differences between groups II and III. The results with VaSera were comparable to those of abiPWV. CONCLUSIONS: Measuring baPWV with the abiPWV is safe and has a similar clinical utility to that of VaSera. Incorporating this function into the options of abiPWV makes it a complete device for assessing arterial stiffness.

Performance assessment of 11 commercial serological tests for SARS-CoV-2 on hospitalised COVID-19 patients.

BACKGROUND: Commercial availability of serological tests to evaluate immunoglobulins (Ig) targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has grown exponentially since the start of the coronavirus disease 2019 (COVID-19) outbreak. Thorough validation of these tests is important before use as epidemiological tools to infer seroprevalence in specific populations and as diagnostic tools to complement molecular approaches (e.g., quantitative reverse transcription-polymerase chain reaction). METHODS: Commercial serological tests from 11 suppliers were assayed side-by-side using 126 samples from SARS-CoV-2-infected inpatients and 36 from healthy and HIV-infected individuals. RESULTS: The majority of the tests assayed have >95% specificity. For the sensitivity calculation, samples were stratified by days since symptoms onset; sensitivity peaks at 16-21 days for IgM and IgA (maximum 91.2%, Euroimmun) and, dependant on the test, at 16-21 or >21 days for IgG (maximum 94.1%, Snibe). Data from semiquantitative tests show that patients with a severe clinical presentation have lower levels of Ig targeting SARS-CoV-2 at <10 days since symptoms onset and higher levels at >21 days, compared to patients with a non-severe presentation. CONCLUSIONS: This study highlights the heterogeneity of sensitivity and generally high specificity of the serological tests and establishes a basis for their usefulness to complement diagnostic techniques and population seroprevalence studies.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability.

BACKGROUND: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. METHODS: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation (P<0.01). CONCLUSIONS: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Altering the time of the second gonadotropin-releasing hormone injection and artificial insemination (AI) during Ovsynch affects pregnancies per AI in lactating dairy cows.

Based on previous research, we hypothesized that Cosynch at 72 h [GnRH-7 d-PGF(2alpha)-72 h-GnRH + artificial insemination (AI)] would result in a greater number of pregnancies per AI (P/AI) than Cosynch at 48 h. Further, we hypothesized that P/AI would be improved to a greater extent when GnRH was administered at 56 h after PGF(2alpha) before AI at 72 h due to a more optimal interval between the LH surge and AI. Nine hundred twenty-seven lactating dairy cows (n = 1,507 AI) were blocked by pen, and pens rotated through treatments. All cows received GnRH followed 7 d later by PGF(2alpha) and then received one of the following: 1) GnRH + timed AI 48 h after PGF(2alpha) (Cosynch-48); 2) GnRH 56 h after PGF(2alpha) + timed AI 72 h after PGF(2alpha) (Ovsynch-56); or 3) GnRH + timed AI 72 h after PGF(2alpha) (Cosynch-72). Pregnancy diagnoses were performed by ultrasound at 31 to 33 d post-AI and again at 52 to 54 d post-AI. Overall P/AI were similar for the Cosynch-48 (29.2%) and Cosynch-72 (25.4%) groups. The Ovsynch-56 group had a greater P/AI (38.6%) than Cosynch-48 or Cosynch-72. Presynchronized first-service animals had greater P/AI than cows at later services in Cosynch-48 (36.2 vs. 23.0%) and Ovsynch-56 (44.8 vs. 32.7%) but not in Cosynch-72 (24.6 vs. 26.2%). Similarly, primiparous cows had greater P/AI than multiparous cows in Cosynch-48 (34.1 vs. 22.9%) and Ovsynch-56 (41.3 vs. 32.6%), but not Cosynch-72 (29.8 vs. 25.3%). In conclusion, we found no advantage to Cosynch at 72 h vs. 48 h. In contrast, we found a clear advantage to treating with GnRH at 56 h, 16 h before a 72-h AI, probably because of more-optimal timing of AI before ovulation.

Exams at classroom have bidirectional effects on the long-term memory of an unrelated graphical task.

The influence of a given event on long-term memory formation of another one has been a relevant topic of study in the neuroscience field in recent years. Students at school learn contents which are usually tested in exam format. However, exam elevates the arousal state of the students acting as a mild stressor that could influence another memory formation ongoing process. Thus, in this study we examine in high school students the effect of exams on long-term retention of unrelated information, learned at different times before or after the exams. Our results show that exams are not innocuous and that they could improve or reduce the retention of temporarily associated content. These effects did not show gender differences. Our findings should alert teachers about the side effects of exams on the learning of other content within the same school day.

Recent Trends in Nanotechnology Toward CNS Diseases: Lipid-Based Nanoparticles and Exosomes for Targeted Therapeutic Delivery.

Central nervous system (CNS) diseases constitute a set of challenging pathological conditions concerning diagnosis and therapeutics. For most of these disorders, there is a lack of early diagnosis, biomarkers to allow proper follow-up of disease progression and effective therapeutic strategies to allow a persistent cure. The poor prognosis of most CNS diseases is, therefore, a global concern, especially regarding chronic age-related neurodegenerative disorders, which are already considered problems of public health due to the increasing average of life expectancy. The difficulties associated with the treatment of CNS diseases are owed, at least in part, to very specific characteristics of the brain and spinal cord, when compared to peripheral organs. In this regard, the CNS is physically and chemically protected by the blood-brain barrier (BBB), which, while maintaining essential brain homeostasis, significantly restricts the delivery of most therapeutic agents to the brain parenchyma. On the other hand, regenerative properties of the tissue are lacking, meaning that a CNS insult resulting in neuronal death is a permanent phenomenon. Approaches for transposing the BBB aiming to treat CNS diseases, relying on specific properties of nanosystems, have been reported for therapeutic delivery to CNS without interfering with the normal function of the brain. In this chapter, we address the latest advances concerning the principles of such approaches, employing lipid-based nanoparticles and cell-produced exosomes as drug and nucleic acid delivery systems, and summarize recent example of applications in the context of neurological diseases. Major achievements obtained in preclinical studies and the trends identified by these studies are emphasized to provide new prospects for further developments in this area, thus enabling us to move from the research realm to the clinical arena.

Dosage compensation in sciarids is achieved by hypertranscription of the single X chromosome in males.

Dosage compensation refers to the process whereby females and males with different doses of sex chromosomes have similar amounts of products from sex chromosome-linked genes. We analyzed the process of dosage compensation in Sciara ocellaris, Diptera of the suborder Nematocera. By autoradiography and measurements of X-linked rRNA in females (XX) and males (XO), we found that the rate of transcription of the single X chromosome in males is similar to that of the two X chromosomes in females. This, together with the bloated appearance of the X chromosome in males, support the idea that in sciarids dosage compensation is accomplished by hypertranscription of the X chromosome in males.