Clinical Observations Research Articles

Clinical observation on treatment of Alzheimer's disease with Sun's scalp-abdominal acupuncture combined with donepezil hydrochloride.

To observe the effect of scalp-abdominal acupuncture combined with donepezil hydrochloride on cognition and life ability of patients with Alzheimer's disease (AD), so as to evaluate its clinical efficacy. Sixty AD patients were collected and randomly divided into control group (30 cases) and observation group (30 cases). Patients in the control group were treated with oral donepezil hydrochloride (5 mg, once daily). Patients in the observation group were treated with scalp-abdominal acupuncture at Baihui (GV20), Yintang (GV24+), Sishencong (EX-HN1), "emotional area", Shenting (GV24), "abdominal area 1""abdominal area 8", and bilateral Fengchi (GB20), Taixi (KI3), Xuanzhong (GB39), Zusanli (ST36) on the basis of control group, and electroacupuncture (10 Hz/50 Hz, 0.5 to 5.0 mA) was applied to EX-HN1, "emotional area""abdominal area 1" and "abdominal area 8", once daily, 30 min each time. Four weeks as a course of treatment, both the two groups were treated for two consecutive courses. Before and after treatment, the mini-mental state examination (MMSE), AD assessmennt scale-cognitive subscale (ADAS-Cog) and activity of daily living scale (ADL) were evaluated. The clinical efficacy index was calculated and safety was evaluated. After treatment, the MMSE and ADL scores were higher (P<0.05) and the ADAS-Cog score was lower (P<0.05) than those before treatment in both groups. Compared with the control group, the MMSE and ADL scores were increased (P<0.05) and ADAS-Cog score was decreased (P<0.05) in the observation group. The total effective rate of the observation group (26/30, 86.67%) was higher (P<0.05) than that of the control group (23/30, 76.67%). No adverse reactions occurred in both groups during the treatment. Scalp-abdominal acupuncture combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of AD patients, and the efficacy is better than that of oral donepezil hydrochloride alone.

Tuberculosis as an interdisciplinary problem: a case of occupational damage to the organs of the genitourinary system

In the Russian Federation, genitourinary tuberculosis ranks third in the structure of extrapulmonary tuberculosis. Timely recognition of genitourinary tuberculosis is usually difficult. The authors analyzed a case of occupational infection with tuberculosis of the genitourinary system by a phthisiologist. The clinical observation ended with a clinical cure for tuberculosis of the genitourinary system, however, with the outcome in chronic prostatitis, chronic post-tuberculosis pyelonephritis with the development of chronic kidney disease. It is shown that the timely establishment of a connection between urinary syndrome and epidemiological, including professional anamnesis, contributes to the timely establishment of the professional nature of the disease. With untimely diagnosis and late initiation of treatment of tuberculosis of the genitourinary system, serious complications can develop up to the destruction of the kidney with complete loss of its function, which leads to disability and loss of ability to work. If tuberculosis of the genitourinary system is suspected, experts recommend conducting a study of urine sediment, prostate secretion to determine the deoxyribonucleic acid of mycobacterium tuberculosis by polymerase chain reaction. Any doubt in case of nonspecific inflammation of the genitourinary system should be interpreted in favor of tuberculosis with further in-depth examination and dynamic monitoring.

Development of Physiologically Based Biopharmaceutical Model (PBBM) for Felodipine Prolonged-Release Tablet as useful tool for prediction of formulation.

Physiologically Based Biopharmaceutical Models (PBBMs) are advanced tools that integrate physiological parameters with drug-specific properties to simulate drug behavior in vivo. In this study, we present the development of a PBBM specifically tailored for felodipine prolonged-release (PR) tablet formulations. Felodipine, a potent calcium channel blocker, is widely used for the treatment of hypertension and angina pectoris. Prolonged-release formulations aim to provide controlled drug release, ensuring sustained therapeutic effect with reduced dosing frequency and minimized adverse effects. Our PBBM incorporates key physiological processes such as gastrointestinal transit, drug dissolution, absorption, distribution, metabolism, and elimination. Data from in vitro dissolution studies, preclinical pharmacokinetics, and clinical observations are integrated to parameterize the model accurately. Special attention is given to the physicochemical properties of felodipine and the release characteristics of the PR tablet formulation. Validation of the PBBM is conducted against clinical pharmacokinetic data obtained from bioequivalence studies and population pharmacokinetic analyses of felodipine PR tablets. The model may demonstrate excellent predictive performance, accurately capturing plasma concentration-time profiles across different dosing regimens and patient populations. The developed PBBM provides valuable insights into the biopharmaceutical behavior of felodipine PR tablets, facilitating rational formulation design, dosage regimen optimization, and therapeutic individualization. It serves as a powerful tool for drug developers, regulatory agencies, and clinicians to enhance the efficiency and effectiveness of drug development and clinical pharmacotherapy

Phototherapeutic keratectomy for cornealepithelial-stromaldystrophies in pediatric patients.

Corneal dystrophies may develop gradually from early onset in childhood and persist for years to decades. Visual impairment or repeated ocular irritations caused by corneal dystrophies severely affect the quality of life. Although various surgical treatment options are indicated for adult patients, the treatment plan for pediatric patients remains unclear. Herein we describe clinical observations of phototherapeutic keratectomy for corneal epithelial-stromal dystrophies in three pediatric patients (five eyes). Corneal opacities were successfully removed, and visual acuity was greatly improved in all operated eyes. The procedure of phototherapeutic keratectomy seems to be feasible in the treatment of corneal epithelial-stromal dystrophies in c hildren, with advantages of minimal invasion and good visual outcomes.

Sclerosing mesenteritis as a surgical problem: a review of the literature and own clinical observation

The problem of studying the pathology of mesenteric fat of the small intestine in surgical practice has not yet received enough attention. A number of questions remain unresolved regarding the etiology and pathogenesis of mesenteric diseases, their possible connection with benign and malignant diseases, methods of their laboratory and instrumental diagnosis, possible options for conservative and surgical treatment, as well as systematization and structuring of the classification. One of the poorly studied representatives of diseases of the mesentery of the small intestine continues to be Sclerosing mesenteritis, characterized by various histological variants of damage to mesenteric fat and a varied nonspecific clinical picture. Taken together, this leads to certain difficulties in diagnosis, patients seeking access to doctors of various profiles, which ultimately negatively affects the results of treatment and can lead to social maladjustment and possible disability. Reports on the occurrence of this pathology in the medical literature are few and, as a rule, describe extremely rare clinical cases. However, in recent years, the frequency of detection of this pathology continues to grow steadily, which is associated with the progressive aging of the population, a high degree of surgical activity in relation to urgent diseases of the abdominal organs, and the improvement of instrumental diagnostic methods. Issues of etiology, pathogenesis, differential diagnosis of this disease and its possible connection with the paraneoplastic process currently continue to cause debate. Further accumulation of clinical experience, a better understanding of the pathogenesis of the disease, and improvement of imaging techniques will allow us to develop clearer diagnostic and clinical criteria, narrow the diagnostic search and, ultimately, improve and standardize treatment. The article provides a review of the literature on this rare surgical pathology, presents our own clinical observation, and discusses diagnostic issues and treatment options for this disease.

Nail growth disorder in multiple fingers following harvesting of radial forearm free flap for phalloplasty in gender-affirming surgery: a case report

Nail growth disturbance commonly takes place after trauma or relevant diseases, such as infections and tumors. However, abnormal growth of the nail plate sometimes occurs without an obvious causative factor. This report presents the case of a patient who underwent male genital reconstruction with a radial forearm free flap for gender affirmation. Although the entire process was smooth, with no accidental events, the second, third, and fourth phalangeal nail plates of the hand from which the flap was harvested showed no evident growth of the fingernail 2 months postoperatively. Nail production was preserved in the remaining fingernails. Typical symptoms, such as redness, swelling, and tenderness, were noted upon clinical observation. Eventually, nail production restarted 5 months after surgery. Steroid and antibiotic treatment was attempted to reduce periungual inflammation. Additionally, close observation with psychological support was conducted.

Abstract B027: The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency

Abstract Methylthioadenosine phosphorylase (MTAP) loss, due to focal homozygous deletions in chromosome 9 (9p21.3), occurs in over 25% of urothelial carcinoma and is an adverse prognostic factor for overall survival. Furthermore, MTAP-deleted tumors are associated with a “cold” tumor immune microenvironment and are resistant to immune checkpoint inhibitor therapy. Loss of MTAP confers a dependency on methionine adenosyltransferase 2A (MAT2A), which catalyzes the production of the primary methyl donor for all cellular methyltransferase reactions, S-adenosyl methionine (SAM). IDE397, a potent small molecule inhibitor of MAT2A, was developed to selectively exploit this synthetic lethal vulnerability in MTAP −/− tumors. The accumulation of the metabolite MTA in MTAP −/− tumors combined with a reduction of SAM by MAT2A inhibition results in selective inhibition of PRMT5, a methyltransferase that governs spliceosome fidelity. This triggers pre-mRNA splicing defects that may induce RNA polymerase stalling and can cause R-loop accumulation. Furthermore, due to essential roles in 1-carbon metabolism, MAT2A inhibition together with MTAP loss leads to depletion of metabolites required for both de novo and salvage nucleotide biosynthesis, thus preventing effective management of DNA replication and DNA damage repair. Notably, R-loops must be resolved by topoisomerase activity (TOP1) to prevent replication conflict and mitotic catastrophe. These combinatorial mechanistic relationships underpin a hypothesis that dual inhibition of MAT2A and TOP1 will fully capitalize on the synthetic lethal vulnerabilities associated with MTAP loss in urothelial cancers (replication stress, genomic instability). Consistent with this, IDE397 in combination with TOP1 inhibitors demonstrated synergistic combination benefit in MTAP −/− bladder cancer cell lines in vitro and in cell-line derived xenograft (CDX) models in vivo. IDE397 exposure was associated with heavily disordered methionine metabolism and accumulation of DNA damage response intermediates. In the ongoing Phase 1 dose escalation/expansion study of IDE397 in MTAP −/− solid tumors (NCT04794699), measurable tumor shrinkage has been observed in urothelial cancers (including a CR per RECIST 1.1) along with molecular responses on serial ctDNA measurements. Supported by our preclinical data, and the clinical observation that MTAP −/− urothelial cancers may be more sensitive to sacituzumab govitecan (SG); a TROP-2-targeting TOP1 ADC (UNITE study; JCO.2023.41.16_suppl.4572), a combination of SG+IDE397 could represent a novel early-line therapy for these patients with high unmet need. We plan to evaluate the combination of SG+IDE397 in MTAP-/- urothelial cancers in the next stage of the ongoing IDE397 trial (NCT04794699). Citation Format: Claire L. Neilan, Marcus M. Fischer, Damien Garbett, Arjun A. Rao, Mili Mandal, Michael A. White, Jasgit C. Sachdev. The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B027.

O21 Raman spectroscopy for detection of squamous cell carcinoma in recessive dystrophic epidermolysis bullosa skin

Abstract Introduction and aims Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disorder caused by biallelic pathogenic variants in COL7A1, which encodes type VII collagen (C7). Lack of C7 leads to blistering, chronic wounds, scarring and early onset of life-shortening squamous cell carcinomas (SCCs). Currently, the suspicion of SCC is mostly determined by clinical observation of visible changes in chronic wounds, and often requires multiple biopsies for histological diagnosis. This project aims to improve clinical care by developing a new noninvasive means of detecting SCC. To achieve this, we used Raman spectroscopy, a nondestructive analytical technique to study the changes occurring in RDEB skin when SCC is present, with the goal of creating a bedside test that can aid clinicians in the early diagnosis of SCC. Methods Raman spectroscopic imaging was performed on 7-µm frozen skin sections from RDEB (n = 3), RDEB SCC (n = 3) and normal skin (n = 3) to identify signalling changes between nonlesional and lesional states. An in-depth molecular composition analysis of the samples was performed using multivariate analysis with the goal of highlighting changes in abundance of specific molecules when SCC is present. Results For both nonmalignant and RDEB SCC skin sites we found specific Raman peaks associated with protein (1004 cm−1, 1650 cm−1) or lipids (1450 cm−1). RDEB SCC indicated a relative increase in DNA and protein. High-quality Raman spectroscopic images could be acquired that showed clear correlation with histological appearances. Current work is under way to determine which specific biological compounds contribute to the Raman spectra observed. Conclusions Raman spectroscopic imaging can provide comprehensive and noninvasive molecular tissue mapping with resolution comparable to histological sections, enabling molecular-based detection of SCC. Future work will focus on characterization of the SCC molecular profile, in addition to determining whether fibre optic Raman spectroscopy can be used to guide the biopsy/resection of RDEB lesions.

Sir William Osler (1849-1919) and neurology in his time.

Sir William Osler, physician in Montreal, in Pennsylvania, at Johns Hopkins and in England, promoted clinical medicine and its interpretation through clinical and pathological observation. He was a keen bibliophile and medical historian. He taught at the bedside and wrote a textbook that was a standard work in his time and for several decades after he died. As a generalist he practised the emerging speciality of neurology and knew many of the early clinicians in that field. The neurology of his time and his contributions to the subject are explored here.

CARDIAC AMYLOIDOSIS IN ELDERLY WITH POSITIVE SCINTIGRAPHY AND MONOCLONALITY: A DIAGNOSTIC DILEMMA

Abstract Background and Aims Clinical identification of elderly patients with both wild–type transthyretin amyloidosis (ATTR) and monoclonal gammopathy of unknown significance (MGUS) is increasing. For this reason, accurate amyloid histologic subtyping is crucial in case of concomitant positivity of bisphosphonate scintigraphy and monoclonal protein testing. We report the diagnostic work–up of cardiac amyloidosis in this specific patient subtype in our tertiary referral center. Methods Among 133 patients who received the diagnosis of cardiac amyloidosis from March 2021 to March 2023, 21 (16%) presented with an abnormality of both bisphosphonate scintigraphy and at least one of the serum monoclonal protein tests. Patients underwent abdominal fat biopsy/needle aspiration as the first diagnostic procedure. In case of negative results, an endomyocardial biopsy (EMB) was planned. Amyloid was identified at histology by Congo Red staining. Amyloid typing was obtained by immunohistochemistry using a recently developed amyloid antibody panel AmYkit (Amimed) applicable on fixed paraffin–embedded tissues in an automated platform. The results were compared with those obtained with standard immunohistochemistry. Results Sixteen of the 21 patients were older than 75 years (76%, 81±10 ys) with a grade 3 (62%) or 2 (33%) scintigraphy. A grade 1 positive scintigraphy was detected in one patient. Serum immunofixation revealed a previously unknown monoclonal protein peak in 78%, while 22% had a history of MGUS. None of the patients had hematologic disorders. TTR pathogenic mutation was detected in one patient. On pathologic examination, abdominal fat was negative for amyloid in all cases, while Congo Red staining was positive in all examined EMBs. Immunohistochemistry performed with standard antibodies was not able to discriminate between AL and ATTR, due to signal overlapping of variable intensity. Conversely, our preliminary results with AmYkit panel of antibodies demonstrate absence of signal overlapping in over 90% of cases, allowing accurate histologic discrimination between AL and TTR. Conclusion Based on our clinical and histologic observations, in elderly patients with concomitant positivity of both bisphosphonate scintigraphy and monoclonal protein testing, TTR is the most frequent type of cardiac amyloid. EMB is a useful diagnostic tool to confirm the clinical suspicion of amyloidosis. Accurate amyloid subtyping is granted by a more sensitive panel of antibodies.

Pre- and postsynaptic signatures in the prelimbic cortex associated with "alcohol use disorder" in the rat.

The transition to alcohol use disorder (AUD) involves persistent neuroadaptations in executive control functions primarily regulated by the medial prefrontal cortex. However, the neurophysiological correlates to behavioral manifestations of AUD are not fully defined. The association between cortical neuroadaptations and behavioral manifestations of addiction was studied using a multi-symptomatic operant model based on the DSM-5 diagnostic criteria for AUD. This model aimed to characterize an AUD-vulnerable and AUD-resistant subpopulation of outbred male Wistar rats and was combined with electrophysiological measurements in the prelimbic cortex (PL). Mirroring clinical observations, rats exhibited individual variability in their vulnerability to develop AUD-like behavior, including motivation to seek for alcohol (crit 1), increased effort to obtain the substance (crit 2), and continued drinking despite negative consequences (crit 3). Only a small subset of rats met all the aforementioned AUD criteria (3 crit, AUD-vulnerable), while a larger fraction was considered AUD-resilient (0 crit). The development of AUD-like behavior was characterized by disruptions in glutamatergic synaptic activity, involving decreased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and heightened intrinsic excitability in layers 2/3 PL pyramidal neurons. These alterations were concomitant with a significant impairment in the ability of mGlu2/3 receptors to negatively regulate glutamate release in the PL but not in downstream regions like the basolateral amygdala or nucleus accumbens core. In conclusion alterations in PL synaptic activity were strongly associated with individual addiction scores, indicating their role as potential markers of the behavioral manifestations linked to AUD psychopathology.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

Assessment of Cefuroxime and Cefuroxime Clavulanic Acid Prescription Practices for Infection Management in Routine Indian Healthcare Settings: Expert Insights

Background: Cefuroxime axetil has shown effectiveness as part of intravenous/oral sequential therapy for community-acquired pneumonia (CAP) treatment, although some countries currently lack dosage recommendations for this regimen. In addition, the perspectives of clinicians were not studied. So, this study evaluated the prescription practice of cefuroxime, and cefuroxime+ clavulanic acid in the management of infections in routine Indian settings. Methods: The cross-sectional survey, titled ‘Cefuroxime &amp; Cefuroxime+Clavulanic acid in Management of Infections: Expert Perspective (CARE) Study’, utilized a 20-item, multiple-response questionnaire to gather expert opinion from specialists regarding the clinical use of cefuroxime and cefuroxime + clavulanic acid in managing infections. The survey encompassed questions about current prescription practices, clinical observations, preferences, and experiences related to the use of these antibiotics in routine settings. Results: Among the 164 clinicians surveyed, 78% of the respondents indicated that cefuroxime was highly effective in managing lower respiratory tract infections. Additionally, 91% of the experts stated that the combination of cefuroxime and clavulanic acid was very effective in managing infections. The majority of clinicians recommended cefuroxime + clavulanic acid as the initial therapy for complicated urinary tract infections (88%), as well as first-line therapy for uncomplicated skin and soft tissue infections (45%) and community-acquired pneumonia (58%). According to 40% of the clinicians, cefuroxime + clavulanic acid was recommended as the initial therapy for 21-30% of patients suspected of methicillin-resistant Staphylococcus aureus infection. Most respondents (88%) preferred cefuroxime + clavulanic acid as the antibiotic for managing Pseudomonas aeruginosa infection. Conclusion: The survey has emphasized the critical role of cefuroxime and cefuroxime + clavulanic acid as antibiotics in managing diverse infections. Clinicians' recognition of their efficacy and preference for combination therapy has underscored the importance of antibiotic stewardship in optimizing patient care.

A mathematical model on the propagation of tau pathology in neurodegenerative diseases.

A system of partial differential equations is developed to study the spreading of tau pathology in the brain for Alzheimer's and other neurodegenerative diseases. Two cases are considered with one assuming intracellular diffusion through synaptic activities or the nanotubes that connect the adjacent cells. The other, in addition to intracellular spreading, takes into account of the secretion of the tau species which are able to diffuse, move with the interstitial fluid flow and subsequently taken up by the surrounding cells providing an alternative pathway for disease spreading. Cross membrane transport of the tau species are considered enabling us to examine the role of extracellular clearance of tau protein on the disease status. Bifurcation analysis is carried out for the steady states of the spatially homogeneous system yielding the results that fast cross-membrane transport combined with effective extracellular clearance is key to maintain the brain's healthy status. Numerical simulations of the first case exhibit solutions of travelling wave form describing the gradual outward spreading of the pathology; whereas the second case shows faster spreading with the buildup of neurofibrillary tangles quickly elevated throughout. Our investigation thus indicates that the gradual progression of the intracellular spreading case is more consistent with the clinical observations of the development of Alzheimer's disease.

Clinical observation of minimally invasive vitrectomy combined with preserving foveal inner boundary membrane in the treatment of macular splits with high myopia.

Clinical observation of minimally invasive vitrectomy combined with preserving foveal inner boundary membrane in the treatment of macular splits with high myopia.

Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures.

Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN. IFALD pathogenesis is complex, depending on the TPN components as well as on the patient's medical conditions. Despite numerous animal studies and clinical observations, the molecular mechanisms driving IFALD remain largely unknown. The present study was set up to elucidate the mechanisms underlying IFALD. For this purpose, human liver spheroid co-cultures were treated with a TPN mixture, followed by RNA sequencing analysis. Subsequently, following exposure to TPN and its single nutritional components, several key events of liver injury, including mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, apoptosis, and lipid accumulation (steatosis), were studied using various techniques. It was found that prolonged exposure to TPN substantially changes the transcriptome profile of liver spheroids and affects multiple metabolic and signaling pathways contributing to liver injury. Moreover, TPN and its main components, especially lipid emulsion, induce changes in all key events measured and trigger steatosis.

Comparative Study of Staphylococcus epidermidis Virulence Profiles in an animal Model of Endophthalmitis

Introduction: Gram-positive staphylococci are responsible for over 90% of cases of postoperative infectious endophthalmitis, with Staphylococcus epidermidis accounting for approximately 70% of isolated microorganisms. Objective: To evaluate the relationship between S. epidermidis virulence and severity of endophthalmitis in an animal model. Methodology: New Zealand albino rabbits were divided into two groups and administered 100 colony-forming units of S. epidermidis strains. In the virulent group, four rabbits received a multi-antibiotic resistant, mecA, ica, and atlE gene carrying S. epidermidis strain, from a patient´s conjuntival microbiota and three a biofilm-forming S. epidermidis ATCC 35984. In the non-virulent group, five rabbits were inoculated with a strain sensitive to all tested antibiotics and lacking mecA, ica, and atlE genes, also from a patient and three rabbits received the non-producer biofilm S. epidermidis ATCC 29122. Clinical and ultrasound examinations were conducted every three hours until endophthalmitis symptoms appeared, followed by daily clinical assessments. Histological evaluations were performed 15 days post-inoculation. Results: The less virulent group displayed milder inflammation and reduced intraocular damage in comparison to the more virulent group based on clinical and ultrasound observations. Nevertheless, histopathological analysis revealed similar inflammation in all groups, 15 days post-inoculation. Discussion: Less virulent S. epidermidis strains induced less severe inflammation as observed through clinical and ultrasound assessments. However, long-term histopathological assessments showed effects comparable to those seen with the more virulent strain.

Biophysics of frequency-dependent variation in paresthesia and pain relief during spinal cord stimulation.

The neurophysiological effects of spinal cord stimulation (SCS) for chronic pain are poorly understood, resulting in inefficient failure-prone programming protocols and inadequate pain relief. Nonetheless, novel stimulation patterns are regularly introduced and adopted clinically. Traditionally, paresthetic sensation is considered necessary for pain relief, although novel paradigms provide analgesia without paresthesia. However, like pain relief, the neurophysiological underpinnings of SCS-induced paresthesia are unknown. Here, we paired biophysical modeling with clinical paresthesia thresholds (of both sexes) to investigate how stimulation frequency affects the neural response to SCS relevant to paresthesia and analgesia. Specifically, we modeled the dorsal column (DC) axonal response, dorsal column nucleus (DCN) synaptic transmission, conduction failure within DC fiber collaterals, and dorsal horn network output. Importantly, we found that high-frequency stimulation reduces DC fiber activation thresholds, which in turn accurately predicts clinical paresthesia perception thresholds. Furthermore, we show that high-frequency SCS produces asynchronous DC fiber spiking and ultimately asynchronous DCN output, offering a plausible biophysical basis for why high-frequency SCS is less comfortable and produces qualitatively different sensation than low-frequency stimulation. Finally, we demonstrate that model dorsal horn network output is sensitive to SCS-inherent variations in spike timing, which could contribute to heterogeneous pain relief across patients. Importantly, we show that model DC fiber collaterals cannot reliably follow high-frequency stimulation, strongly affecting network output and typically producing anti-nociceptive effects at high frequencies. Altogether, these findings clarify how SCS affects the nervous system and provide insight into the biophysics of paresthesia generation and pain relief.Significance Statement The effects of spinal cord stimulation (SCS) on the nervous system are poorly understood, resulting in inadequate clinical success rates. Here, we use a biophysical modeling approach to investigate the neural response to SCS. We demonstrate that low- and high-frequency stimulation produce contrasting responses in the dorsal columns, brainstem, and dorsal horn. Importantly, our modeling approach was able to accurately predict clinical paresthesia thresholds as a function of frequency, as well as provide plausible biophysical explanations for frequency-dependent effects on paresthesia quality and pain relief. Overall, our results greatly enhance our understanding of the neural response to SCS, thereby offering context for interpreting clinical observations and crucial insight for development of future SCS systems.

Comparison of the recovery characteristics for canine corneal ulcer treated with corneoconjunctival transposition or conjunctival autografts

Corneal ulceration induced by Staphylococcus pseudintermedius (S. pseudintermedius) is a common clinical eye disease. Antibiotics combined with corneoconjunctival transposition (CCT) or conjunctival autografts (CA) are often used, but the recovery characteristics are still unknown. In this experiment, canine corneal ulcer models induced by S. pseudintermedius and treated with levofloxacin eye drops (LED) were created. The models were used to compare the recovery characteristics of CCT and CA, combined with LED, by clinical observation, histopathology, and cytokine expression detected by qRT-PCR analysis. The results showed that the ulcerative cornea with only LED treatment perforated after 48 h. The mRNA expression of TLR2, IL-1β, IL-6, IL-8, and TNF-α genes was significantly elevated on 14, 28, and 35 days after the surgery compared to normal (p < 0.01). On day 42, the inflammatory damage had resolved, but the corneal transparency and arrangement of collagen fibrils in the CCT group were higher than those in the CA group. The mRNA expression of EGF, FGF, TGF-β1 and VEGF genes increased significantly (p < 0.01), mostly until day 42, proving that CCT and CA surgery contributed to the corneal recovery, and relieved the inflammatory reaction, with the elimination of corneal cicatrices needing a period of reconstruction. Therefore, this study has provided, for the first time, the method for establishing a canine corneal ulcer model induced by S. pseudintermedius. More importantly, the recovery of canine ulcerative corneas with CCT or CA surgery is reported for the first time.

T84 Monolayer Cell Cultures Support Productive HBoV and HSV-1 Replication and Enable In Vitro Co-Infection Studies

T84 Monolayer Cell Cultures Support Productive HBoV and HSV-1 Replication and Enable In Vitro Co-Infection Studies