Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation. METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS. RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10-39; OR = 4.73, p = 2 × 10-10; OR = 2.3, p = 7.49 × 10-9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10-7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10-16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10-6). CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.

Effectiveness and one-year whiteness stability of different in-office bleaching agents and alternative protocols.

STATEMENT OF PROBLEM: In-office bleaching has been widely researched. However, few studies have evaluated alternative protocols for this procedure. Moreover, information on the long-term stability of in-office whitening is limited. PURPOSE: The purpose of this in vitro study was to evaluate the effectiveness and 1-year stability of in-office bleaching with 35% hydrogen peroxide (35%HP) and 37% carbamide peroxide (37%CP) using traditional and alternative protocols. MATERIAL AND METHODS: Forty human third molars were stained with tea and allocated to groups (n=10). Traditional protocols consisted of 3 applications of 35%HP for 15 minutes and 1 application of 37%CP for 45 minutes. Alternative protocols consisted of 1 application of 35%HP for 45 minutes and 3 applications of 37%CP for 45 minutes. Protocols were applied for 3 weeks. CIELab color coordinates were measured at baseline and weekly during treatment and at 1-week, 6-month, and 1-year follow-ups. Effectiveness and stability of the bleaching treatments were interpreted using 50:50% perceptibility and acceptability thresholds. CIELab, chroma, hue angle, and whiteness index were analyzed using the Wilcoxon signed-rank test (α=.05). RESULTS: All protocols showed improvement in bleaching after the first week (P≤.005). All bleaching procedures presented excellent whitening outcomes. Alternative protocols showed a larger rebound effect after 1 year, indicating less stability. For the whiteness index, no differences between the completion of the treatments and 1-year follow-up was found for the bleaching treatments and protocols (P>.05), except for the 37%CP alternative protocol (P=.005). CONCLUSIONS: All tested protocols presented excellent effectiveness in bleaching. Traditional protocols exhibited a greater whiteness stability, while the alternative protocols showed a greater rebound effect after 1 year.

Clinical characteristics and outcomes of aortic prosthetic valve endocarditis: comparison between transcatheter and surgical bioprostheses.

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

Optical fiber sensor for water velocity measurement in rivers and channels.

In this work, optical fiber Bragg grating sensors were used to measure water velocity and examine how it was distributed in open channels. Several types of coatings were incorporated into the design of the sensors to examine their effects on the strain that the fibers experienced as a result of the water flow. Due to their low elastic coefficient, which reduced the hysteresis, the results indicated that the aluminum- and acrylate-coated fibers had the best performance. ANSYS-CFX V2020 R2 software was used to model the strain encountered by the fibers under various flow rates to assess the performance of the FBG sensors. The calculations and actual data exhibited good convergence, demonstrating the accuracy of the FBG sensors in determining water velocity. The study illustrated the usability of the proposal in both scenarios by contrasting its application in rivers and channels.

Search for Biomarkers for the LC-ESI-QqQ Determination of Phenoxymethylpenicillin Treatment in Raw or Cooked Chicken Meat Samples.

The high standards required for food safety make it necessary to trace unambiguously raw or cooked food products coming from medicated animals. Nevertheless, considering the lability of ß-lactams and their degradation, the detection of the presence of antibiotics in meat either raw or submitted to a cooking process is not easily affordable. To achieve this goal, an evaluation of the effect of common domestic cooking procedures, such as boiling and grilling, on the fate of phenoxymethylpenicillin (PENV) residues was performed. Finally, in this work, the penilloic acid from PENV (MET02) and the corresponding penicilloic acid (PENV-HYDRO) are suggested as biomarkers. These compounds present the highest relative abundances 5 days after the treatment was stopped (5PT) and show enough thermal stability to be considered suitable biomarker candidates for the pharmacological treatment instead of the parent compound. Nevertheless, the peaks corresponding to MET02 are significantly more intense than those for PENV-HYDRO, which makes preferential the use of MET02 to perform the control of samples.

Influence of base designs on the manufacturing accuracy of vat-polymerized diagnostic casts using two different technologies.

STATEMENT OF PROBLEM: Diagnostic casts can incorporate different base designs and be manufactured using different vat-polymerization technologies. However, the influence of the interrelation between the base design and the 3D printing technology on the casts' final accuracy remains unclear. PURPOSE: The purpose of this in vitro study was to assess the influence of different base designs of 3D printed casts on the accuracy of 2 vat-polymerization technologies. MATERIAL AND METHODS: A digital maxillary cast was obtained and used to generate 3 different base designs: solid (S group), honeycombed (HC group), and hollow (H group). The HC and H groups were subdivided based on the wall thickness of the cast design, resulting in 2 subgroups with thicknesses of 1 mm (HC1 and H1) and 2 mm (HC2 and H2) (N=100, n=10). Eleven reference cubes were added to each specimen for subsequent measurements. Specimens were manufactured by using 2 vat-polymerization 3D printers: Nextdent 5100 (ND group) and Sonic Mini 4K (SM4K group) and a resin material suitable for both 3D printers (Nextdent Model 2.0). A coordinate measuring machine quantified the linear and 3-dimensional discrepancies between the digital cast and each reference specimen. Trueness was defined as the average absolute dimensional discrepancy between the virtual cast and the specimens produced through additive manufacturing (AM), while precision was delineated as the standard deviation in dimensional discrepancies between the digital cast and the AM specimens. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U pairwise comparison tests (α=.05). RESULTS: For the NextDent group the trueness ranged from 21.83 µm to 28.35 µm, and the precision ranged from 17.82 µm to 37.70 µm. For the Phrozen group, the trueness ranged from 45.15 µm to 64.51 µm, and the precision ranged from 33.51 µm to 48.92 µm. The Kruskal-Wallis test showed significant differences on the x-, y-, and z-axes and in the 3D discrepancy (all P<.001). On the x-axis, the Mann-Whitney U test showed significant differences for the Phrozen group between the H-2 and H-1 groups (P=.001), H-2 and S groups (P<.001), and HC-2 and S groups (P=.012). On the y-axis, significant differences were found in the Phrozen group between the H-2 and H-1 groups (P=.001), the H-2 and S, H-1 and HC-1, and HC-1 and S groups (P<.001), the H-1 and HC-2 groups (P=.007), and the HC-2 and S groups (P=.009). The NextDent group exhibited significant differences, particularly among the HC-1 and H-2 groups (P=.004), H-1 (P=.020), and HC-2 (P=.001) groups; and on the z-axis significant differences were found in the Phrozen group between the H-2 and H-1 and S groups and the HC-2 group and H-1 and S groups (both P<.001). In the NextDent group, significant differences were found between the H-2 and HC-2 (P=.047) and HC-1 (P=.028) groups. For the 3D discrepancy analysis, significant differences were found in the Phrozen group between the H-2 and H-1 and S groups (P<.001), the H-1 and HC-2 groups (P=.001), the S and HC-1 and HC-2 groups (P<.001), and the H-1 and HC-1 groups (P=.002). In the NextDent group, significant differences were observed between the H-2 and HC-1 groups (P=.012). CONCLUSIONS: The accuracy of digital casts depends on the manufacturing trinomial and base design of the casts. The honeycomb and hollow based designs provided the highest accuracy in the NextDent and Phrozen groups respectively for the material polymer tested. All specimens fell in the clinically acceptable range.

New developments in infective endocarditis.

Infective endocarditis is a continually evolving disease. Present-day patients differ significantly from those treated a few decades ago: they tend to be older and have more comorbidities and health care-related episodes, while new groups of patients have emerged with new types of endocarditis, such as those affecting patients with percutaneous valve prostheses. There have also been changes in diagnostic techniques. Although transthoracic and transesophageal echocardiography are still the most commonly used imaging modalities, other techniques, such as 3-dimensional transesophageal ultrasound, cardiac computed tomography, and nuclear medicine tests (PET/CT and SPECT/CT), are increasingly used for diagnosing both the disease and its complications. In recent years, there have also been significant developments in antibiotic therapy. Currently, several treatment strategies are available to shorten the hospital phase of the disease in selected patients, which can reduce the complications associated with hospitalization, improve the quality of life of patients and their families, and reduce the health care costs of the disease. This review discusses the main recent epidemiological, diagnostic and therapeutic developments in infective endocarditis.

Effect of Myxoma Virus Species Jump on Iberian Hare Populations.

The myxoma virus species jump from European rabbits (Oryctolagus cuniculus) to Iberian hares (Lepus granatensis) has raised concerns. We assess the decline suffered by Iberian hare populations on the Iberian Peninsula and discuss the association between the effect of myxomatosis and the average abundance index, which we estimated by using hunting bags.

Donor Lung Preservation at 10°C: Clinical and Logistical Impact.

INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

Bioequivalence risk assessment of oral formulations containing racemic ibuprofen through a chiral physiologically based pharmacokinetic model of ibuprofen enantiomers.

The characterization of the time course of ibuprofen enantiomers can be useful in the selection of the most sensitive analyte in bioequivalence studies. Physiologically based pharmacokinetic (PBPK) modelling and simulation represents the most efficient methodology to virtually assess bioequivalence outcomes. In this work, we aim to develop and verify a PBPK model for ibuprofen enantiomers administered as a racemic mixture with different immediate release dosage forms to anticipate bioequivalence outcomes based on different particle size distributions. A PBPK model incorporating stereoselectivity and non-linearity in plasma protein binding and metabolism as well as R-to-S unidirectional inversion has been developed in Simcyp®. A dataset composed of 11 Phase I clinical trials with 54 scenarios (27 per enantiomer) and 14,452 observations (7129 for R-ibuprofen and 7323 for S-ibuprofen) was used. Prediction errors for AUC0-t and Cmax for both enantiomers fell within the 0.8-1.25 range in 50/54 (93 %) and 42/54 (78 %) of scenarios, respectively. Outstanding model performance, with 10/10 (100 %) of Cmax and 9/10 (90 %) of AUC0-t within the 0.9-1.1 range, was demonstrated for oral suspensions, which strongly supported its use for bioequivalence risk assessment. The deterministic bioequivalence risk assessment has revealed R-ibuprofen as the most sensitive analyte to detect differences in particle size distribution for oral suspensions containing 400 mg of racemic ibuprofen, suggesting that achiral bioanalytical methods would increase type II error and declare non-bioequivalence for formulations that are bioequivalent for the eutomer.

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Breasts as a perceived barrier to physical activity in Mexican women: A cross-sectional study.

BACKGROUND: Scarce evidence exists on barriers to physical activity in Mexican women. Despite evidence from other countries, no research has investigated the influence of the breast on PA in this population. OBJECTIVE: To determine the association between the breast and physical activity in Mexican women. DESIGN: Cross-sectional observational study. METHODS: Volunteers were 279 Mexican women from Veracruz, Durango, and Baja California states, who completed a paper survey of their demographics, brassiere characteristics, breast pain, and frequency and amounts of weekly physical activity. RESULTS: The first barrier to physical activity was time constraints, followed by breast-related issues. Breast pain was reported by 47.1% of women, and the breast as a barrier to physical activity participation was reported by 30.6%. Responses, such as "I am embarrassed by excessive breast movement" and "My breasts are too big" were the most frequently reported breast-related barriers to physical activity. Breast pain was associated with the menstrual cycle and exercise. Breast health knowledge and pain intensity were unrelated to moderate- and vigorous-intensity physical activity. The 36.4% and 6.7% of women did not meet weekly moderate- and vigorous-intensity physical activity guidelines, respectively. Weekly moderate- and vigorous-intensity physical activity was similar between women reporting breast pain and those who did not. CONCLUSIONS: Because the breast was the second most significant barrier to physical activity, it is imperative to increase breast health knowledge in Mexican women to reduce impediments to physical activity.

Perception of Mexican women regarding their breasts as a barrier to physical activityPhysical activity provides numerous health benefits, sometimes associated with reversing or delaying several diseases. However, barriers to increasing physical activity in women remain, as the breast is an anatomical aspect that is unique to women. Breast pain has been reported in more than 50% of women who perform physical exercise. Therefore, the study aimed to determine the associations between breast characteristics and barriers to physical activity in Mexican women. Two hundred and seventy-nine women from three Mexican states voluntarily participated in the study. They answered survey questions on the history of bra use, barriers to physical activity, and essential demographic characteristics. The main findings of this study were that issues related to the breasts were reported as the second barrier to physical activity participation. In addition, time constraints were reported as the main reason impeding physical activity participation. Public health initiatives should support attempts to increase breast satisfaction among women of all breast sizes to stimulate engagement in physical activity throughout their lives.

Effects of the COVID-19 pandemic on gestational diabetes in Castilla-La Mancha (Spain).

SUBJECT-MATTER: To assess the effect of the 2019 coronavirus (COVID-19) pandemic on gestational diabetes (GDM). MATERIAL AND METHODS: In this retrospective, multicentre, non-interventional study carried out in Castilla-La Mancha, Spain, we compared 663 women with GDM exposed to the pandemic (pandemic group), with 622 women with GDM seen one year earlier (pre-pandemic group). The primary endpoint was a Large for Gestational Age (LGA) newborn as an indicator of poor GDM control. Secondary endpoints included obstetric and neonatal complications. RESULTS: During the pandemic, the gestational week at diagnosis (24.2 ±â€¯7.4 vs 22.9 ±â€¯7.7, p = 0.0016) and first visit to Endocrinology (26.6 ±â€¯7.2 vs 25.3 ±â€¯7.6, p = 0.0014) were earlier. Face-to-face consultations were maintained in most cases (80.3%). The new diagnostic criteria for GDM were used in only 3% of cases. However, in the pandemic group, the final HbA1c was higher (5.2 ±â€¯0.48 vs 5.29 ±â€¯0.44%, p = 0.047) and there were more LGA newborns (8.5% vs 12.8%, p = 0.015). There were no differences in perinatal complications. CONCLUSIONS: Care for GDM in our Public Health System did not significantly deteriorate during the COVID-19 pandemic. However, this did not prevent a higher number of LGA newborns.

Superficial vein thrombosis and its relationship with malignancies: a prospective observational study.

BACKGROUND: The interrelation of cancer with venous thromboembolism is established, yet the specific impact on the incidence and progression of superficial vein thrombosis (SVT) remains unclear. OBJECTIVES: To investigate the association between SVT and malignancies, focusing on risk factors, presentation, course and complications. METHODS: A single-center prospective observational study of patients diagnosed with DVT or SVT referred to a venous thromboembolism clinic between January 2013 and April 2018. RESULTS: Of the 632 patients, 205 presented with SVT at referral, 16.6% having active cancer. Significant associations were found between active cancer and the risk of developing proximal SVT (RR 1.54 [1.18-2.03] p < 0.01), SVT within 3 cm from junction (RR 2.01 [1.13-3.72] p = 0.019), bilateral SVT (RR 8.38 [2.10-33.43] p < 0.01) and SVT affecting multiple veins (RR 2.42 [1.40-4.20] p < 0.01), with a higher risk of persistence (RR 1.51 [1.18-1.95] p < 0.01) and progression (RR 5.75 [2.23-14.79] p < 0.01) at initial assessment. Patients with SVT and no malignancy history demonstrated an elevated risk for new-onset cancer during follow-up (RR 1.43 [1.13-1.18] p = 0.022), especially in cases of proximal or bilateral SVT, initial progression or subsequent DVT or PE. No significant differences were observed in persistence, recurrence or complications during initial evaluation or follow-up across different pharmacological treatments. CONCLUSIONS: Research suggests a probable link between cancer history and the development of SVT. SVT presented more severely in cancer patients. SVT, especially in its more complex forms, could serve as a predictive marker for the future development of cancer. Treatment approaches varied, no significant differences in outcomes were noted.

Coherent activity within and between hemispheres: cortico-cortical connectivity revealed by rTMS of the right posterior parietal cortex.

Introduction: Low frequency (1 Hz) repetitive transcranial stimulation (rTMS) applied over right posterior parietal cortex (rPPC) has been shown to reduce cortical excitability both of the stimulated area and of the interconnected contralateral homologous areas. In the present study, we investigated the whole pattern of intra- and inter-hemispheric cortico-cortical connectivity changes induced by rTMS over rPPC. Methods: To do so, 14 healthy participants underwent resting state EEG recording before and after 30 min of rTMS at 1 Hz or sham stimulation over the rPPC (electrode position P6). Real stimulation was applied at 90% of motor threshold. Coherence values were computed on the electrodes nearby the stimulated site (i.e., P4, P8, and CP6) considering all possible inter- and intra-hemispheric combinations for the following frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-50 Hz). Results and discussion: Results revealed a significant increase in coherence in delta, theta, alpha and beta frequency bands between rPPC and the contralateral homologous sites. Moreover, an increase in coherence in theta, alpha, beta and gamma frequency bands was found between rPPC and right frontal sites, reflecting the activation of the fronto-parietal network within the right hemisphere. Summarizing, subthreshold rTMS over rPPC revealed cortico-cortical inter- and intra-hemispheric connectivity as measured by the increase in coherence among these areas. Moreover, the present results further confirm previous evidence indicating that the increase of coherence values is related to intra- and inter-hemispheric inhibitory effects of rTMS. These results can have implications for devising evidence-based rehabilitation protocols after stroke.

Clinical Profile and Prognosis of Patients with Left-Sided Infective Endocarditis with Surgical Indication Who Are Not Operated.

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.