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Brain Stimulation Jun 2024Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation...
BACKGROUND
Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons.
METHODS
In 25 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment.
RESULTS
We observed an early positive EEG deflection starting after approx. 2 ms followed by a series of superimposed peaks with an inter-peak interval of ∼1.1-1.4 ms in multiple electrodes surrounding the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1 region and was modified by changes in stimulation intensity and current direction.
DISCUSSION
Single-pulse TMS of the M1 evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts.
PubMed: 38909748
DOI: 10.1016/j.brs.2024.06.008 -
The Journal of Pain Jun 2024Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated....
Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated. Previous research suggested both, central and peripheral mechanisms, with the latter involving the influence of specific A-delta-fibers. Therefore, this study aimed to investigate the influence of a non-ischaemic A-fiber conduction blockade on the OA response in healthy participants. A total of 52 participants were recruited for an A-fiber conduction blockade via compression of the superficial radial nerve. To monitor fiber-specific peripheral nerve conduction capacity, quantitative sensory testing was performed continuously. Before, during and after the A-fiber block, an individualized OA-paradigm was applied to the dorsum of both hands (blocked and control side were randomized). Pain intensity of each heat stimulus was evaluated by an electronic visual analogue scale. A successful A-fiber conduction blockade was achieved in thirty participants. Offset analgesia has been verified within time (before, during, after blockade), and condition (blocked and control side) (p < 0.01, d > 0.5). Repeated measurements ANOVA showed no significant interaction effects between OA within condition and time (p = 0.24, η² = 0.05). Hence, no significant effect of A-fiber blockade was detected on OA during noxious heat stimulation. The results suggest that peripheral A-fiber afferents may play a minor role in OA compared to alternative central mechanisms or other fibers. However, further studies are needed to substantiate a central rather than peripheral influence on OA. PERSPECTIVE: This article presents the observation of offset analgesia before, during and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of offset analgesia and endogenous pain modulation in general may help to explain the underlying aspects of pain disorders.
PubMed: 38908497
DOI: 10.1016/j.jpain.2024.104611 -
Farmacia Hospitalaria : Organo Oficial... Jun 2024To describe, analyze and compare the situation of pharmaceutical care consultations for outpatients with immune-mediated inflammatory diseases of the Pharmacy Services...
OBJECTIVE
To describe, analyze and compare the situation of pharmaceutical care consultations for outpatients with immune-mediated inflammatory diseases of the Pharmacy Services of Spain at two different times.
METHOD
Longitudinal, multicenter and unidisciplinary descriptive observational study, carried out by the Immune-mediated Inflammatory Diseases Working Group of the Spanish Society of Hospital Pharmacy through a virtual survey in 2019 and 2021. Variables were collected regarding coordination, resources, biosimilars, unmet needs and telepharmacy. Numerical results were presented in absolute value and percentage and free text responses were grouped by topic areas. To compare the results between the two collection times, the Chi-Square test was used with a significance level of p<0.05.
RESULTS
The level of participation was 70 pharmacists in 2019 and 53 in 2021. The main significant findings obtained were an increase in participation in asthma biologic committees (p=0.044) and care coordination in dermatology (p=0.003) and digestive system (p=0.022). The wide use of biosimilar biological medicines stood out, with a 15% increase in the exchange of the reference biological to the biosimilar. The lack of research in the field and insufficient human resources, among other unmet needs, were revealed. In the outpatient units, the use of the stratification model of the MAPEX project was a minority and an increase in the use of information and communication technologies was promoted. Motivated by the pandemic derived from COVID-19, telepharmacy was established for the first time in 85% of the centers, maintaining the service at 66% at the time of the second survey.
CONCLUSIONS
Outpatient units are undergoing constant change to adapt to new times, for which institutional support is needed to invest more resources to promote the development of strategies to reduce unmet needs. We must continue working to achieve a pharmaceutical practice that provides efficiency, safety, quality of life and access to innovative drugs in patients with immune-mediated inflammatory diseases.
PubMed: 38906719
DOI: 10.1016/j.farma.2024.05.005 -
European Journal of Surgical Oncology :... Jun 2024Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been...
First-line palliative systemic therapy alternated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: A single-arm phase II trial (CRC-PIPAC-II).
BACKGROUND
Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy.
METHODS
This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m) with intravenous leucovorin (20 mg/m) and 5-fluorouracil (400 mg/m). Primary outcome were major treatment-related adverse events. Secondary outcomes included minor events, tumor response, progression-free survival (PFS) and overall survival (OS).
RESULTS
Twenty patients completed 52 treatment cycles. Fifteen major events occurred in 7 patients (35 %): 5 events (33 %) related to systemic therapy; 5 (33 %) related to ePIPAC; and 5 (33 %) were biochemical events. No treatment-related deaths occurred. All patients experienced minor events, mostly abdominal pain, nausea and peripheral sensory neuropathy. After treatment, radiological, pathological, cytological, and biochemical response was observed in 0 %, 88 %, 38 %, and 31 % of patients respectively. Curative surgery was achieved in one patient. Median PFS was 10.0 months (95 % confidence interval [CI] 8.0-13.0) and median OS was 17.5 months (95 % CI 13.0-not reached).
CONCLUSIONS
Combining palliative systemic therapy with oxaliplatin-based ePIPAC in patients with unresectable CPM was feasible and showed an acceptable safety profile. Treatment-induced response and survival are promising, yet further research is required to determine the additional value of ePIPAC to systemic therapy.
PubMed: 38905732
DOI: 10.1016/j.ejso.2024.108487 -
Journal of Acquired Immune Deficiency... Jul 2024Scientific evidence indicates that HIV viral suppression to an undetectable level eliminates sexual transmission risk ("Undetectable=Untransmittable" or "U=U"). However,...
BACKGROUND
Scientific evidence indicates that HIV viral suppression to an undetectable level eliminates sexual transmission risk ("Undetectable=Untransmittable" or "U=U"). However, U=U messaging has been met with skepticism among sexual minority men (SMM) and others. In this survey-based experiment, we manipulated messaging about HIV risk and examined reactions and perceived message accuracy among US SMM.
METHODS
SMM living with HIV (n = 106) and HIV-negative/status-unknown SMM (n = 351) participated in an online survey (2019-2020). Participants were randomly assigned to 1 of 3 messaging conditions, which varied by level of HIV sexual transmission risk associated with an undetectable viral load (No Risk [U=U]/Low Risk/Control). Participants reported reactions, message accuracy, and reasons for perceiving inaccuracy. We coded open-response data (reactions and reasons) into conceptual categories (eg, "Enthusiasm"). We compared reactions, accuracy ratings, and reasons by condition and serostatus.
RESULTS
In the No Risk Condition, common reactions were Enthusiasm (40.0%), Skepticism/Disagreement (20.0%), and Agreement (19.4%), reactions common to comparison conditions. A higher percentage of HIV-negative/status-unknown participants (24.1%) expressed Skepticism/Disagreement in the No Risk Condition compared with other conditions (3.2%-9.7%). Participants living with HIV were more likely than HIV-negative/status-unknown participants to perceive the message as accurate in all conditions. In the No Risk Condition, common reasons for perceiving inaccuracy were Risk Misstated (46.1%), Oversimplified/Caveats Needed (17.1%), and Personal Unfamiliarity/Uncertainty (14.5%), reasons common to comparison conditions. Across conditions, 10.3% of participants attributed message inaccuracy to undetectable being misdefined.
CONCLUSION
Most SMM reacted favorably to U=U messaging. However, many-especially HIV-negative/status-unknown SMM-expressed skepticism. Interventions are needed to enhance U=U understanding and acceptance.
Topics: Humans; Male; HIV Infections; Sexual and Gender Minorities; Adult; Viral Load; United States; Middle Aged; Young Adult; Surveys and Questionnaires; Sexual Behavior
PubMed: 38905477
DOI: 10.1097/QAI.0000000000003417 -
Polish Journal of Microbiology Jun 2024Negative Pressure Wound Therapy (NPWT) has been widely adopted in wound healing strategies due to its multimodal mechanism of action. While NPWT's positive impression on...
Negative Pressure Wound Therapy (NPWT) has been widely adopted in wound healing strategies due to its multimodal mechanism of action. While NPWT's positive impression on wound healing is well-established, its effect on bacterial load reduction remains equivocal. This study investigates NPWT's efficacy in reducing bioburden using an porcine skin model, focusing on the impact of and . Custom-made negative pressure chambers were employed to apply varying negative pressures. Porcine skin was cut into 5 × 5 cm squares and three standardized wounds of 6 mm each were created using a biopsy punch. Then, wounds were infected with and bacterial suspensions diluted 1:10,000 to obtain a final concentration of 1.5 × 10 CFU/ml and were placed in negative pressure chambers. After incubation, bacterial counts were expressed as colony-forming units (CFU) per ml. For at 120 hours, the median CFU, mean area per colony, and total growth area were notably lower at -80 mmHg when compared to -250 mmHg and -50 mmHg, suggesting an optimal negative pressure for the pressure-dependent inhibition of the bacterial proliferation. While analyzing at 120 hours, the response to the negative pressure was similar but less clear, with the minor CFU at -100 mmHg. The influence of intermittent negative pressure on the growth showed notably lower median CFU with the interval therapy every hour compared to the control group. This study contributes valuable insights into NPWT's influence on the bacterial load, emphasizing the need for further research to reformulate its role in managing contaminated wounds.
Topics: Staphylococcus epidermidis; Animals; Swine; Negative-Pressure Wound Therapy; Staphylococcus aureus; Wound Healing; Bacterial Load; Wound Infection; Kinetics; Staphylococcal Infections; Skin
PubMed: 38905277
DOI: 10.33073/pjm-2024-018 -
Frontiers in Public Health 2024Heart failure (HF) risk is greater in rural versus urban regions in the United States (US), potentially due to differences in healthcare coverage and access. Whether...
BACKGROUND
Heart failure (HF) risk is greater in rural versus urban regions in the United States (US), potentially due to differences in healthcare coverage and access. Whether this excess risk applies to countries with universal healthcare is unclear and the underlying biological mechanisms are unknown. In the prospective United Kingdom (UK) Biobank, we investigated urban-rural regional differences in HF risk and the mechanistic role of biological aging.
METHODS
Multivariable Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to residential urban-rural region and a Biological Health Score (BHS) that reflects biological aging from environmental, social, or dietary stressors. We estimated the proportion of the total effect of urban-rural region on HF mediated through BHS.
RESULTS
Among 417,441 European participants, 10,332 incident HF cases were diagnosed during the follow-up. Compared to participants in large urban regions of Scotland, those in England/Wales had significantly increased HF risk (smaller urban: HR = 1.83, 95%CI: 1.64-2.03; suburban: HR = 1.77, 95%CI: 1.56-2.01; very rural: HR = 1.61, 95%CI: 1.39-1.85). Additionally, we found a dose-response relationship between increased biological aging and HF risk (HR = 1.14 (95%CI: 1.12-1.17). Increased biological aging mediated a notable 6.6% ( < 0.001) of the total effect of urban-rural region on HF.
CONCLUSION
Despite universal healthcare in the UK, disparities in HF risk by region were observed and may be partly explained by environmental, social, or dietary factors related to biological aging. Our study contributes to precision public health by informing potential biological targets for intervention.
Topics: Humans; Heart Failure; United Kingdom; Female; Male; Middle Aged; Aged; Rural Population; Prospective Studies; Aging; Risk Factors; Urban Population; Proportional Hazards Models; Adult
PubMed: 38903584
DOI: 10.3389/fpubh.2024.1381146 -
Diseases of the Colon and Rectum Jun 2024Longitudinal studies on functional outcome after colon resection are limited.
BACKGROUND
Longitudinal studies on functional outcome after colon resection are limited.
OBJECTIVE
Examine bowel dysfunction and related distress one and three years after colon resection utilizing the low anterior resection syndrome score as well as specific validated items.
DESIGN
This study presents the long-term results of bowel dysfunction and related distress based on the quality of life in colon cancer study, an observational, prospective multicenter study of patients with newly diagnosed colon cancer.
SETTINGS
The study was conducted at 21 Swedish and Danish surgical centers between 2015 and 2019.
PATIENTS
All patients who underwent right- or left-sided colon resection were considered eligible. Exclusion criteria were age below 18, cognitive impairment or inability to understand Swedish/Danish. Patients completed extensive questionnaires at diagnosis, and after one and three years. Clinical data were supplemented by national quality registries.
MAIN OUTCOME MEASURES
The low anterior resection syndrome score, specific bowel symptoms and the patient-reported distress were assessed.
RESULTS
Of 1,221 patients (83% response rate), 17% reported major LARS one year after either type of resection, consistent at 3 years (17% right, 16% left). In the long-term, the only significant difference between types of resection was a high occurrence of loose stools following right-sided resections. Overall, less than one-fifth of patients experienced distress, with women reporting more frequent symptoms and greater distress. In particular, incontinence and loose stools correlated strongly with distress.
LIMITATIONS
Absence of pre-diagnosis bowel function data.
CONCLUSIONS
Our study indicates that bowel function remains largely intact following colon resection, with only a minority reporting significant distress. Adverse outcomes were more common among women. The occurrence of loose stools following right-sided resection and the association between incontinence, loose stools, and distress highlights a need for postoperative evaluations and more thorough assessments beyond the LARS score when evaluating colon cancer patients. See Video Abstract.
PubMed: 38902840
DOI: 10.1097/DCR.0000000000003358 -
Scientific Reports Jun 2024Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer....
Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.
Topics: Humans; Antigens, Bacterial; DNA Damage; RNA, Long Noncoding; Bacterial Proteins; Helicobacter pylori; Stomach Neoplasms; Cell Movement; Cell Line, Tumor; Helicobacter Infections; Rad51 Recombinase; Tumor Suppressor Protein p53; Histones
PubMed: 38902391
DOI: 10.1038/s41598-024-65221-y -
ACS Nano Jun 2024Two-dimensional (2D) van der Waals (vdWs) heterojunctions have been actively investigated in low-power-consumption and fast-response photodiodes owing to their...
Two-dimensional (2D) van der Waals (vdWs) heterojunctions have been actively investigated in low-power-consumption and fast-response photodiodes owing to their atomically smooth interfaces and ultrafast interfacial charge transfer. However, achieving ultralow dark current and ultrafast photoresponse in the reported photovoltaic devices remains a challenge as the large built-in electric field in a heterojunction can not only speed up photocarrier transport but also increase the minority-carrier dark current. Here, we propose a high-spike barrier photodiode that can achieve both an ultralow dark current and an ultrafast response. The device is fabricated by the Te/WS heterojunction, while the band alignment can transition from type-II to type-I with a high electron barrier and a large hole built-in electronic field. The high electron barrier can greatly reduce the drift current of minority carriers and the generation current of the thermal carriers, while the large built-in electronic field can still speed up the photocarrier transport. The designed Te/WS vdWs photodiode yields an ultralow dark current of 8 × 10 A and an ultrafast photoresponse of 10/13 μs. Furthermore, a high-performance visible-light imager with a pixel resolution of 100 × 40 is demonstrated using the Te/WS vdWs photodiode. This work provides a comprehensive understanding of designing 2D-material-based photovoltaics with excellent overall performance.
PubMed: 38902201
DOI: 10.1021/acsnano.4c03729