Decoding the Reference Letter: Strategies to Reduce Unintentional Gender Bias in Letters of Recommendation.

Introduction: There is a growing body of literature on gender bias in letters of recommendation (LORs) in academic medicine and the negative effect of bias on promotion and career advancement. Thus, increasing knowledge about gender bias and developing skills to mitigate it is important for advancing gender equity in medicine. This workshop aims to provide participants with knowledge about linguistic bias (focused on gender), how to recognize it, and strategies to apply to mitigate it when writing LORs. Methods: We developed an interactive 60-minute workshop for faculty and graduate medical education program directors consisting of didactics, reflection exercises, and group activities. We used a postworkshop survey to evaluate the effectiveness of the workshop. Descriptive statistics were used to analyze Likert-scale questions and a thematic content analysis for open-ended prompts. Results: We presented the workshop four times (two local and two national conferences) with one in-person and one virtual format for each. There were 50 participants who completed a postworkshop survey out of 74 total participants (68% response rate). Ninety-nine percent of participants felt the workshop met its educational objectives, and 100% felt it was a valuable use of their time. Major themes described for intended behavior change included utilization of the gender bias calculator, mindful use and balance of agentic versus communal traits, closer attention to letter length, and dissemination of this knowledge to colleagues. Discussion: This workshop was an effective method for helping participants recognize gender bias when writing LORs and learn strategies to mitigate it.

Electromagnetic Field Stimulation Therapy for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative dementia worldwide. AD is a multifactorial disease that causes a progressive decline in memory and function precipitated by toxic beta-amyloid (Aß) proteins, a key player in AD pathology. In 2022, 6.5 million Americans lived with AD, costing the nation $321billion. The standard of care for AD treatment includes acetylcholinesterase inhibitors (AchEIs), NMDA receptor antagonists, and monoclonal antibodies (mAbs). However, these methods are either: 1) ineffective in improving cognition, 2) unable to change disease progression, 3) limited in the number of therapeutic targets, 4) prone to cause severe side effects (brain swelling, microhemorrhages with mAb, and bradycardia and syncope with AchEIs), 5) unable to effectively cross the blood-brain barrier, and 6) lack of understanding of the aging process on the disease. mAbs are available to lower Aß, but the difficulties of reducing the levels of the toxic Aß proteins in the brain without triggering brain swelling or microhemorrhages associated with mAbs make the risk-benefit profile of mAbs unclear. A novel multitarget, effective, and safe non-invasive approach utilizing Repeated Electromagnetic Field Stimulation (REMFS) lowers Aß levels in human neurons and memory areas, prevents neuronal death, stops disease progression, and improves memory without causing brain edema or bleeds in AD mice. This REMFS treatment has not been developed for humans because current EMF devices have poor penetration depth and inhomogeneous E-field distribution in the brain. Here, we discussed the biology of these effects in neurons and the design of optimal devices to treat AD.

Detection of mecA Genes in Hospital-Acquired MRSA and SOSA Strains Associated with Biofilm Formation.

Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of ß-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% ß-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community.

Aptamers: A Cutting-Edge Approach for Gram-Negative Bacterial Pathogen Identification.

Early and accurate diagnoses of pathogenic microorganisms is essential to correctly identify diseases, treating infections, and tracking disease outbreaks associated with microbial infections, to develop precautionary measures that allow a fast and effective response in epidemics and pandemics, thus improving public health. Aptamers are a class of synthetic nucleic acid molecules with the potential to be used for medical purposes, since they can be directed towards any target molecule. Currently, the use of aptamers has increased because they are a useful tool in the detection of specific targets. We present a brief review of the use of aptamers to detect and identify bacteria or even some toxins with clinical importance. This work describes the advances in the technology of aptamers, with the purpose of providing knowledge to develop new aptamers for diagnoses and treatment of different diseases caused by infectious microorganisms.

TIPS en pacientes cirróticos con trombosis venosa portal: una revisión de la literatura / TIPS in cirrhotic patients with portal vein thrombosis: A review of the literature

En los últimos años, la trombosis de la vena porta entre los pacientes cirróticos se ha comportado como una entidad reconocida y cada vez más estudiada, no solo por su creciente incidencia, sino por la asociación con gravedad y mal pronóstico en cirrosis. Asimismo, se hacen objeto de estudio las terapias disponibles para el manejo tanto médico como quirúrgico de estos pacientes, lo que ha dado un papel importante a la derivación portosistémica transyugular intrahepática (TIPS). El uso de TIPS en esta población se posiciona como una alternativa de manejo aceptable, no solo por brindar mejoría en las complicaciones derivadas de la hipertensión portal, sino también por sus resultados prometedores en diferentes estudios sobre el flujo y la recanalización portal, y por su perfil de seguridad. Sin embargo, la eficacia, los efectos adversos a largo plazo y el pronóstico de dicha intervención en la compleja fisiopatología de la cirrosis deben continuar en estudio. El objetivo de este artículo es revisar los avances del uso de TIPS en el manejo de pacientes con cirrosis hepática y trombosis portal.

In recent years, portal vein thrombosis among cirrhotic patients has been a well-recognized and continuously studied entity, not only because of its increasing incidence but also because of its association with severity and poor prognosis in cirrhosis. Likewise, therapies available for both medical and surgical management in these patients are being studied, which has given an important role to the transjugular intrahepatic portosystemic shunt (TIPS). The use of TIPS in this population is positioned as an acceptable management alternative, not only because it provides improvement in complications derived from portal hypertension, but also because of its promising results in different studies on portal flow and recanalization upgrade, and for its safety. However, the efficacy, long-term adverse effects, and prognosis of this intervention in the complex pathophysiology of cirrhosis must continue to be studied. The objective of this article is to review the advances in the use of TIPS in the management of patients with liver cirrhosis and portal vein thrombosis.

Perioperative Regional Anesthesia Pain Outcomes in Children: A Retrospective Study of 3160 Regional Anesthetics in Routine Practice.

OBJECTIVE: Randomized controlled trials indicate regional anesthesia (RA) improves postoperative outcomes with reduced pain and opioid consumption. Therefore, we hypothesized children who received RA, regardless of technique, would have reduced pain/opioid use in routine practice. METHODS: Using a retrospective cohort, we assessed the association of RA with perioperative outcomes in everyday practice at our academic pediatric hospital. Patients 18 years or below undergoing orthopedic, urologic, or general surgeries with and without RA from May 2014 to September 2021 were categorized as single shot, catheter based, or no block. Outcomes included intraoperative opioid exposure and dose, preincision anesthesia time, postanesthesia care unit (PACU) opioid exposure and dose, PACU antiemetic/antipruritic administration, PACU/inpatient pain scores, PACU/inpatient lengths of stay, and cumulative opioid exposure. Regression models estimated the adjusted association of RA with outcomes, controlling for multiple variables. RESULTS: A total of 11,292 procedures with 3160 RAs were included. Compared with no-block group, single-shot and catheter-based blocks were associated with opioid-free intraoperative anesthesia and opioid-free PACU stays. Post-PACU (ie, while inpatient), single-shot blocks were not associated with improved pain scores or reduced opioid use. Catheter-based blocks were associated with reduced PACU and inpatient opioid use until 24 hours postop, no difference in opioid use from 24 to 36 hours, and a higher probability of use from 36 to 72 hours. RA was not associated with reduced cumulative opioid consumption. DISCUSSION: Despite adjustment for confounders, the association of RA with pediatric pain/opioid use outcomes was mixed. Further investigation is necessary to maximize the benefits of RA.

Hop, Skip, and Jump: Hydrogen Molecular Transport through Amorphous Polyethylene Matrices Studied via Molecular Dynamics Simulations.

In the pursuit of advancing and diversifying energy technologies for a more sustainable future, the possibilities of hydrogen (H2) usage will broaden, as will our understanding of its containment materials. Polyethylene (PE) has a vast assortment of uses and applications, which are growing with demands for alternative energy possibilities. One use of PE liner is as a prime candidate for nonmetallic piping and pressurized type IV storage devices. Such applications require PE to effectively prevent H2 transport through containment systems. To study the molecular transport mechanism of hydrogen through polymeric barriers, a system containing hydrogen molecules absorbed within amorphous PE is modeled here using molecular dynamics simulations. The simulations are conducted within a range of temperatures that span the glass transition temperature of amorphous PE. The simulated PE displays bulk density, radius of gyration, and self-diffusion coefficient that are consistent with experimental data. The simulated trajectories are interrogated to study the movement of the guest gas molecules. The results show that the diffusion coefficients increase with temperature, as expected. However, the mobility of the PE chains is found to affect the mobility of absorbed H2 molecules to a much lower extent than it affects that of CH4 molecules because of the much smaller size of the former than of the latter guest. From a molecular perspective, a "hopping" mechanism is observed, according to which H2 molecules hop between one vacant free volume space to another within the polymer matrix, in combination with longer, straight, undisturbed "jumps" or "skips" along directions aligned with regions of ordered PE chains. This suggests that the orientation of the crystallites within the semicrystalline PE matrix affects the H2 containment. Implications of these findings toward PE usage as containment material are discussed.

Bifidobacterium longum LBUX23 Isolated from Feces of a Newborn; Potential Probiotic Properties and Genomic Characterization.

Bifidobacterium longum is considered a microorganism with probiotic potential, which has been extensively studied, but these probiotic effects are strain dependent. This work aims to characterize the probiotic potential, based on the biochemical and genomic functionality, of B. longum LBUX23, isolated from neonates' feces. B. longum LBUX23 contains one circular genome of 2,287,838 bp with a G+C content of 60.05%, no plasmids, no CRISPR-Cas operon, possesses 56 tRNAs, 9 rRNAs, 1 tmRNA and 1776 coding sequences (CDSs). It has chromosomally encoded resistance genes to ampicillin and dicloxacillin, non-hemolytic activity, and moderate inhibition of Escherichia coli ATCC 25922 and to some emergent pathogen's clinical strains. B. longum LBUX23 was able to utilize lactose, sucrose, fructooligosaccharides (FOS), and lactulose. The maximum peak of bacterial growth was observed in sucrose and FOS at 6 h; in lactose and lactulose, it was shown at 8 h. B. longum LBUX23 can survive in gastrointestinal conditions (pH 4 to 7). A decrease in survival (96.5 and 93.8%) was observed at pH 3 and 3.5 during 120 min. argC, argH, and dapA genes could be involved in this tolerance. B. longum LBUX23 can also survive under primary and secondary glyco- or tauro-conjugated bile salts, and a mixture of bile salts due to the high extracellular bile salt hydrolase (BSH) activity (67.3 %), in taurocholic acid followed by taurodeoxycholic acid (48.5%), glycocholic acid (47.1%), oxgall (44.3%), and glycodeoxycholic acid (29.7%) probably due to the presence of the cbh and gnlE genes which form an operon (start: 119573 and end: 123812). Low BSH activity was determined intracellularly (<7%), particularly in glycocholic acid; no intracellular activity was shown. B. longum LBUX23 showed antioxidant effects in DPPH radical, mainly in intact cells (27.4%). In the case of hydroxyl radical scavenging capacity, cell debris showed the highest reduction (72.5%). In the cell-free extract, superoxide anion radical scavenging capacity was higher (90.5%). The genome of B. longum LBUX23 contains PNPOx, AhpC, Bcp, trxA, and trxB genes, which could be involved in this activity. Regarding adherence, it showed adherence up to 5% to Caco-2 cells. B. longum LBUX23 showed in vitro potential probiotic properties, mainly in BSH activity and antioxidant capacity, which indicates that it could be a good candidate for antioxidant or anti-cholesterol tests using in vivo models.

Isolation and Identification of Multidrug-Resistant Klebsiella pneumoniae Clones from the Hospital Environment.

Global dispersion, hospital outbreaks, and lineage relationships between emerging antibiotic-resistant strains such as Klebsiella pneumoniae are of public health interest. This study aimed to isolate and identify K. pneumoniae clones from third-level healthcare hospitals in Mexico to establish their multidrug-resistant phenotype, phylogeny, and prevalence. Biological and abiotic surface samples were used to isolate K. pneumoniae strains and to test their antibiotic susceptibility to classify them. The housekeeping genes: gapA, InfB, mdh, pgi, phoE, ropB, and tonB were used for multilocus sequence typing (MLST). Phylogenetic networks were constructed with 48 strains. Isolated strains (93) were mainly from urine and blood, 96% were resistant to ampicillin as expected, 60% were extended-spectrum ß-lactamases (ESBL), 98% were susceptible to ertapenem and meropenem and 99% were susceptible to imipenem, 46% were multi-drug resistant (MDR), 17% were extensively-drug resistant (XDR), 1% were pan-drug resistant (PDR), and 36% were not classified. The tonB, mdh, and phoE genes were the most variable, and the InfB gene showed positive selection. The most prevalent sequence types (STs) were ST551 (six clones), ST405 (six clones), ST1088 (four clones), ST25 (four clones), ST392 (three clones), and ST36 (two clones). ST706 was PDR, and ST1088 clones were MDR; neither of these STs has been reported in Mexico. The strains analyzed were from different hospitals and locations; thus, it is important to maintain antibiotic surveillance and avoid clone dissemination to prevent outbreaks, adaptation to antibiotics, and the transmission of antibiotic resistance.

Numerical Modeling and Computer Simulation of a Meander Line Antenna for Alzheimer's Disease Treatment, a Feasibility Study.

Alzheimer's disease (AD) is a brain disorder that eventually causes memory loss and the ability to perform simple cognitive functions; research efforts within pharmaceuticals and other medical treatments have minimal impact on the disease. Our preliminary biological studies showed that Repeated Electromagnetic Field Stimulation (REFMS) applying an EM frequency of 64 MHz and a specific absorption rate (SAR) of 0.4 - 0.9 W/kg decrease the level of amyloid-ß peptides (Aß), which is the most likely etiology of AD. This study emphasizes uniform E/H field and SAR distribution with adequate penetration depth penetration through multiple human head layers driven with low input power for safety treatments. In this work, we performed numerical modeling and computer simulations of a portable Meander Line antenna (MLA) to achieve the required EMF parameters to treat AD. The MLA device features a low cost, small size, wide bandwidth, and the ability to integrate into a portable system. This study utilized a High-Frequency Simulation System (HFSS) in the design of the MLA with the desired characteristics suited for AD treatment in humans. The team designed a 24-turn antenna with a 60 cm length and 25 cm width and achieved the required resonant frequency of 64 MHz. Here we used two numerical human head phantoms to test the antenna, the MIDA and spherical head phantom with six and seven tissue layers, respectively. The antenna was fed from a 50-Watt input source to obtain the SAR of 0.6 W/kg requirement in the center of the simulated brain tissue layer. We found that the E/H field and SAR distribution produced was not homogeneous; there were areas of high SAR values close to the antenna transmitter, also areas of low SAR value far away from the antenna. This paper details the antenna parameters, the scattering parameters response, the efficiency response, and the E and H field distribution; we presented the computer simulation results and discussed future work for a practical model.

Pramipexole inhibits formalin-induce acute and long-lasting mechanical hypersensitivity via NF-kB pathway in rats.

Pain is one of the most frequent causes for patients to seek medical care. It interferes with daily functioning and affects the quality of life of the patient. There is a clear need to investigate nonopioid or non-nonsteroidal anti-inflammatory drug alternatives for the treatment of pain. In this study, we determined the effect of acute pre- and posttreatment with pramipexole (PPX), a dopamine D2/D3 selective agonist, on formalin 1%-induced acute and long-lasting nociceptive behavior sensitivity in rats. Moreover, we sought to investigate whether the antiallodynic and antihyperalgesic effect induced by PPX was mediated through the nuclear factor-κB (NF-kB) signaling pathway. Moreover, acute systemic pretreatment with PPX (1 and 3 mg/kg, ip) suppressed the formalin-induced nociceptive behavior during both phases of the formalin test and the development of formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Acute systemic posttreatment with PPX (3 mg/kg, ip) reverted the formalin-induced long-lasting secondary mechanical allodynia and hyperalgesia. Furthermore, PPX inhibits the protein expression of NF-κB-p65 and the levels of tumor necrosis factor-α and interleukin-1ß in the spinal cord of animals with secondary mechanical allodynia and hyperalgesia induced by formalin. These data suggest that PPX has a potential role in producing anti-inflammatory activity. Moreover, the antiallodynic and antihyperalgesic effects induced by PPX can be mediated through the NF-kB signaling pathway.

Association of Race and Ethnicity with Pediatric Postoperative Pain Outcomes.

INTRODUCTION: Inequitable variability in healthcare practice negatively affects patient outcomes. Children of color may receive different analgesic medications in the perioperative period, resulting in different outcomes. METHODS: Medical records of children 0 to ≤ 18 years old from May 2014 to August 2019 were reviewed. The exposure was racial or ethnic groups: Asian, Black, Hispanic, Pacific Islander, and White non-Hispanic (reference). PRIMARY OUTCOME: post-anesthesia care unit mean pain score. SECONDARY OUTCOMES: inpatient mean pain score; opioid, antiemetic, and antipruritic administration in the post-anesthesia care unit and inpatient ward. The association of race or ethnicity with outcomes was modeled using multilevel logistic regression, adjusting for confounders and covariates. RESULTS: Twenty-nine thousand six hundred fourteen cases are included. In the post-anesthesia care unit, Black, Hispanic, and Pacific Islander children had no significant difference in the odds of receiving opioids or having moderate-severe pain as compared to White non-Hispanic patients; Asian children had lower odds of receiving opioids and lower odds of having a moderate-severe mean pain score. In the inpatient setting, Black, Hispanic, and Pacific Islander children had no significant difference in the odds of receiving opioids or having moderate severe-pain as compared to White non-Hispanic children, but Asian children had lower odds of receiving opioids and of having a moderate-severe mean pain score. CONCLUSIONS: Asian children had lower odds of receiving opioids and having moderate-severe pain postoperatively compared to the White non-Hispanic children. These differences may be a function of variation in patient/caregivers culture or healthcare provider care and warrant further investigation.

Local seed sourcing for sustainable forestry.

Seed sourcing strategies are the basis for identifying genetic material meeting the requirements of future climatic conditions and social demands. Specifically, local seed sourcing has been extensively promoted, based on the expected adaptation of the populations to local conditions, but there are some limitations for the application. We analyzed Strict-sense local and Wide-sense local (based on climatic similarity) seed sourcing strategies. We determined species and genetic pools based on these strategies for 40 species and deployment zones in Spain. We also obtained the total number of seed sources and stands for these species in the EU countries. We analyzed the richness of the pools, the relationship with variables related to the use of the species in afforestation, and the availability of seed production areas approved for the production of reproductive material destined to be marketed. This study confirms the existence of extensive species and genetic local pools. Also, that the importance of these pools differs for different species, limitations being derived from the use of forest reproductive material and the existence of approved basic materials. Strategies derived from local seed sourcing approaches are the basis for the use of forest reproductive material because a large number of the species in the area considered in the study are under regulation. However, despite the extensive work done to approve basic materials, limitations based on the availability of seed production areas to provide local material for sustainable forestry are found in those species. Considering a Wide-sense local seed sourcing strategy we provide alternative pools in order to meet social demands under the actual regulations on marketing of reproductive materials.

Insights into the Social Determinants of Health in Older Adults.

In this paper, we review the social determinants of health in older adults and their complex interrelationship with medical diseases. Also, we provide recommendations to address these determinants in the integrated healthcare plan. The social determinants in older adults and its influence in health outcomes have been studied for decades. There is solid evidence for the interrelationship between social factors and the health of individuals and populations; however, these studies are unable to define their complex interrelatedness. Health is quite variable and depends on multiple biological and social factors such as genetics, country of origin, migrant status, etc. On the other hand, health status can affect social factors such as job or education. Addressing social determinants of health in the integrated healthcare plan is important for improving health outcomes and decreasing existing disparities in older adult health. We recommend a person-centered approach in which individualized interventions should be adopted by organizations to improve the health status of older adults at the national and global level. Some of our practical recommendations to better address the social determinants of health in clinical practice are EHR documentation strategies, screening tools, and the development of linkages to the world outside of the clinic and health system, including social services, community activities, collaborative work, and roles for insurance companies.

Genomic and Biochemical Characterization of Bifidobacterium pseudocatenulatum JCLA3 Isolated from Human Intestine.

Bifidobacteria have been investigated due to their mutualistic microbe-host interaction with humans throughout their life. This work aims to make a biochemical and genomic characterization of Bifidobacterium pseudocatenulatum JCLA3. By multilocus analysis, the species of B. pseudocatenulatum JCLA3 was established as pseudocatenulatum. It contains one circular genome of 2,369,863 bp with G + C content of 56.6%, no plasmids, 1937 CDSs, 54 tRNAs, 16 rRNAs, 1 tmRNA, 1 CRISPR region, and 401 operons predicted, including a CRISPR-Cas operon; it encodes an extensive number of enzymes, which allows it to utilize different carbohydrates. The ack gene was found as part of an operon formed by xfp and pta genes. Two genes of ldh were found at different positions. Chromosomally encoded resistance to ampicillin and cephalothin, non-hemolytic activity, and moderate inhibition of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 6538 were demonstrated by B. pseudocatenulatum JCLA3; it can survive 100% in simulated saliva, can tolerate primary and secondary glyco- or tauro-conjugated bile salts but not in a mix of bile; the strain did not survive at pH 1.5-5. The cbh gene coding to choloylglycine hydrolase was identified in its genome, which could be related to the ability to deconjugate secondary bile salts. Intact cells showed twice as much antioxidant activity than debris. B. pseudocatenulatum JCLA3 showed 49% of adhesion to Caco-2 cells. The genome and biochemical analysis help to elucidate further possible biotechnological applications of B. pseudocatenulatum JCLA3.

The attitudes of mental health professionals on the employability of people with mental illness: A different view limiting employment rehabilitation.

OBJECTIVES: Mental health professionals are becoming increasingly involved in the process of employment rehabilitation of persons with psychiatric disabilities. However, few studies address the attitudes of these professionals toward the employability of those with mental illness. The aim of this research was to identify differences in the attitudes of medical and non-medical mental health professionals, as well as to detect any association between attitude scores and the type of professional. METHODS: A sample of 140 employees from public and third sector mental health organizations answered a questionnaire using a scale measuring their attitudes and views on the employability of people with psychiatric disabilities. The psychometric characteristics of the scale are provided together with the variations detected in the professionals' attitudes. RESULTS: This research shows that significant differences in the attitudes between medical and non-medical mental health employees exist and that there is a need for the implementation of educational programs that may help to improve the attitudes of medical professionals toward the employability of people with mental illness. CONCLUSION: This research indicates the importance of improving the professionals' attitudes to support people attempting to return to work.

Numerical Analysis and Design of an EMF Birdcage Wearable Device for the Treatment of Alzheimer's Disease: A Feasibility Study.

In this study, we performed a numerical analysis of a novel EMF Birdcage wearable device for the treatment of Alzheimer's disease (AD). We designed the new device to generate and radiate a frequency of 64 MHz and a specific absorption rate (SAR) of 0.6 W/kg to a simulated human brain tissue. We determined these parameters from our experimental studies on primary human brain cultures at the Indiana University School of Medicine (IUSM). We found that this frequency and SAR decreased the toxic Aß levels in the cell cultures. The frequency of 64 MHZ has good skin depth penetration, which will easily pass through the various head layers, including hair, skin, fat, dura, the cerebrospinal (CSF), and grey matter, and reach deeply into the brain tissues. The SAR of 0.6 W/kg was achieved with lower power input and energy, decreasing the probability of thermal injury. Therefore, these parameters enhance the safety of these potential treatments. This Birdcage device emulates a small-scale MRI machine, producing the same 64 MHz frequency at much lower operating input power. In this work, we utilized a high-frequency simulation system (HFSS/EMPro) software to produce the birdcage structure for the required EMF parameters. The 64 MHz radiating frequency produced the scattering S11 parameter of -15 dbs. We obtained a SAR of 0.6 W/kg when an input power of 100 W was applied. The coil dimensions were found to be near 15 cm in height and 22 cm in diameter, which fits in wearable systems. We found that the distribution of the electric field and SAR radiate homogeneously over the simulated human head with good penetration into the brain, which proves to be an appropriate potential therapeutic strategy for Alzheimer's disease.

EMF Antenna Exposure on a Multilayer Human Head Simulation for Alzheimer Disease Treatments.

In this paper, we follow up with our preliminary biological studies that showed that Repeated electromagnetic field stimulation (REMFS) decreased the toxic amyloid-beta (Aß) levels, which is considered to be the cause of Alzheimer's disease (AD). The REMFS parameters of these exposures were a frequency of 64 MHz and a Specific absorption rate (SAR) of 0.4 to 0.9 W/Kg in primary human neuronal cultures. In this work, an electromagnetic field (EMF) model was simulated using high-frequency simulation system (HFSS/EMPro) software. Our goal was to achieve the EM parameters (EMF Frequency and SAR) required to decrease the toxic Aß levels in our biological studies in a simulated human head. The simulations performed here will potentially lead to the successful development of an exposure system to treat Alzheimer's disease patients. A popular VFH (very high frequency) patch microstrip antenna system was considered in the study. The selection was based on simple and easy construction and appropriateness to the VHF applications. The evaluation of the SAR and temperature distribution on the various head layers, including skin, fat, dura, the cerebrospinal (CSF), and grey matter, brain tissues, were determined for efficacy SAR and safety temperature increase on a simulated human head. Based on a current pulse of 1 A peak current fed to the antenna feeder, a maximum SAR of 0.6 W/Kg was achieved. A range of 0.4 to 0.6 SAR was observed over the various layers of the simulated human head. The initial design of the antenna indicated an antenna size in the order of 1 m in length and width, suggesting a stationary practical model for AD therapy. Future direction is given for wearable antenna and exposure system, featuring high efficiency and patient comfort.

Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases.

We provide a multidimensional sequence of events that describe the electromagnetic field (EMF) stimulation and biological system interaction. We describe this process from the quantum to the molecular, cellular, and organismal levels. We hypothesized that the sequence of events of these interactions starts with the oscillatory effect of the repeated electromagnetic stimulation (REMFS). These oscillations affect the interfacial water of an RNA causing changes at the quantum and molecular levels that release protons by quantum tunneling. Then protonation of RNA produces conformational changes that allow it to bind and activate Heat Shock Transcription Factor 1 (HSF1). Activated HSF1 binds to the DNA expressing chaperones that help regulate autophagy and degradation of abnormal proteins. This action helps to prevent and treat diseases such as Alzheimer's and Parkinson's disease (PD) by increasing clearance of pathologic proteins. This framework is based on multiple mathematical models, computer simulations, biophysical experiments, and cellular and animal studies. Results of the literature review and our research point towards the capacity of REMFS to manipulate various networks altered in aging (Reale et al. PloS one 9, e104973, 2014), including delay of cellular senescence (Perez et al. 2008, Exp Gerontol 43, 307-316) and reduction in levels of amyloid-ß peptides (Aß) (Perez et al. 2021, Sci Rep 11, 621). Results of these experiments using REMFS at low frequencies can be applied to the treatment of patients with age-related diseases. The use of EMF as a non-invasive therapeutic modality for Alzheimer's disease, specifically, holds promise. It is also necessary to consider the complicated and interconnected genetic and epigenetic effects of the REMFS-biological system's interaction while avoiding any possible adverse effects.