Alternative Therapy Research Articles

Utilization of traditional Chinese medicine in the management of cutaneous ulceration induced by cervical lymph node metastasis in tonsillar carcinoma: A case report

ObjectiveCutaneous ulcers induced by metastasis present a challenging clinical issue, often resistant to conventional dressing change interventions. In this case, we demonstrates the efficacy of Traditional Chinese Medicine in managing ruptured tumors. Case presentationWe present a case study of a 40-year-old Chinese male patient diagnosed with advanced tonsillar squamous cell carcinoma with cervical lymph node metastasis and cutaneous ulceration. Despite nearly six months of conventional dressing treatment yielding minimal improvement, significant healing of the ulcerated surface of the neck metastasis was observed after approximately two months of decoction therapy. The cancerous lesion exhibited a reduction of nearly 90 %, with concomitant alleviation of secondly symptoms such as cold intolerance, excessive sweating, anxiety and depression. ConclusionsIn this case, we introduces Traditional Chinese Medicine may be an effective alternative therapy for the treatment of cancer-related disease. And it may also be an optional therapeutic approach for healthcare practitioners with cutaneous carcinoma ulceration.

A Study on Dysmenorrhea and Its Self-Care Behaviors Among Women of Reproductive Age in Tiruvallur District, Tamil Nadu.

Menstrual cramps, which can be categorized as primary or secondary depending on the etiology, are a painful feature of dysmenorrhea.Researchers from throughout the country found that self-care practices for dysmenorrhea included reducing physical activity, adjusting diet, medications, or treatments, adopting alternative therapies, recording symptom clusters of discomforts, and expressing feelings. Methodology:There were 246 women in the reproductive age range who took part in this study. Thiruvallur district's Thirumazhisai town panchayat served as the location of a community-based cross-sectional study.Parameters such as menstrual history, food history, self-care techniques during dysmenorrhea, and sociodemographic information were evaluated using a pre-tested semi-structured questionnaire. The prevalence of dysmenorrhea was found to be 71.54%. Among 47.15% of the participants, 75.8% who were married were found to have dysmenorrhea, whereas 67.7% of the 52.54% participants who were unmarried had dysmenorrhea. The association between age, smoking habits, exercise, and the presence of dysmenorrhea was found to be statistically significant. Women, especially in India, have certain taboos and misconceptions associated with menstruation which can hurt their hygiene and self-care practices. This study highlights the need for menstrual hygiene awareness among women and proper self-care methods to be followed.

Clinical significance of analysis of long non-coding RNA PSMB8-AS1, MBNL1-AS1, and OLMALINC expression by polymerase chain reaction in non-small cell lung cancer

Rationale: Long non-coding RNAs (lncRNAs) influence tumor cell properties during the onset and progression of lung malignancies; however, their diagnostic and prognostic significance has not been determined. We have previously shown that when non-small cell lung cancer (NSCLC) cells acquire a more malignant phenotype (under the influence of macrophagal cytotoxic activity) compared to the original cell lines, the expression of several lncRNAs, in particular PSMB8-AS1, MBNL1-AS1, and OLMALINC, is altered compared to the original cell lines. Aim: A comparative analysis of lncRNAs PSMB8-AS1, MBNL1-AS1, and OLMALINC expression in tissue samples from lung tumors and conditionally normal areas of the lungs and an assessment of the lncRNAs clinical significance. Methods: We have analyzed surgical samples of the tumor and conditionally normal tissue from 16 patients with a verified diagnosis of NSCLC. The expression level of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was assessed by real-time polymerase chain reaction. To analyze the long-term treatment results and clinical significance of the studied genes, the patients were divided into two comparison groups depending on the relative level of lncRNAs expression (above or below the median). Results: The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC in the lung tumor tissue was significantly reduced compared to the conditionally normal tissues (p = 0.0034; p = 0.002 and p = 0.0172, respectively). Analysis of the association between the expression of these lncRNAs with clinical and morphological characteristics, such as disease stage, tumor size, presence of regional and distant metastases was unable to identify any regular patterns. The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was not a significant prognostic factor (p = 0.364; p = 0.759 and p = 0.184, respectively). However in the case of high OLMALINC and PSMB8-AS1 expression, median survival was 47 months, while in the case of their low expression, median survival was not achieved during the follow-up. The expression of lncRNA PSMB8-AS1 in NSCLC tumors positively correlated with the expression of lncRNA OLMALINC (r = 0.680, p = 0.007), which may indicate their functional interplay or the presence of common regulatory mechanisms. Conclusion: The NSCLC tumors demonstrated aberrant expression of PSMB8-AS1, MBNL1-AS1, and OLMALINC lncRNAs. A more detailed study of their expression in various cell types and their regulatory role would allow for validation of new therapeutic targets in NSCLC, as well as for development of alternative therapies.

Percutaneous Tibial Nerve Stimulation's Impact on Sexual Function in Female Patients with Neurogenic Detrusor Overactivity, Sexual Dysfunction, and Multiple Sclerosis.

Background/Objectives: Multiple sclerosis (MS) frequently results in both urinary and sexual dysfunction, which significantly impairs quality of life. Conventional treatments for bladder dysfunction often prove insufficient, leading to the exploration of alternative therapies such as percutaneous tibial nerve stimulation (PTNS). This study aimed to assess the impact of PTNS on sexual function and bladder symptoms in female MS patients with neurogenic detrusor overactivity (NDO) and female sexual dysfunction (FSD). Methods: A total of 65 female MS patients with NDO were evaluated and underwent 12 weeks of standardized PTNS treatment. Sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R), while bladder symptoms were evaluated using the OAB-v8 questionnaire. Participants were grouped based on the presence of sexual dysfunction and distress and compared to a control group of 20 patients who declined PTNS. Results: Significant improvements were observed in FSFI scores across multiple domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) in the treatment groups (p < 0.05). Additionally, 58.46% of patients showed positive responses to PTNS regarding overactive bladder symptoms (OAB-v8 score), while the control group showed no significant changes. Conclusions: PTNS appears to be an effective therapeutic option for improving sexual function and urinary symptoms in female MS patients with NDO and FSD, offering a promising non-invasive alternative for managing these conditions.

Infusion Reactions With Alternative Therapies During the National Shortage of Iron Dextran.

Prior to the national shortage of iron dextran in early 2023, it was the most commonly administered intravenous iron infusion at our institution. After the shortage impacted the health system, alternatives such as iron sucrose and sodium ferric gluconate/sucrose were required that utilized lower doses given at more frequent patient visits. Coinciding with their more prevalent use, an increase in iron infusion reactions was observed. Our study analyzed 880 patients who received iron infusions in three Henry Ford Hospital clinics in metropolitan Detroit, Michigan, from July 2022-June 2023. The 74 reactions that occurred were most commonly associated with iron sucrose at the 500 mg dose (41/74, 55.41%, p < 0.0001). Most reactions observed across all iron formulations and doses were mild, with 83.7% being Grade 0 or 1 as defined by the United States Drug Allergy Registry (USDAR) grading scale for immediate reactions. Patients who experienced an infusion reaction were less likely to complete their infusion plans (OR 0.004 for iron dextran, OR 0.128 for iron sucrose, p < 0.0001), with infusions most commonly being completely discontinued thereafter, with a minority pursuing alternative options. More patients with lower number of doses scheduled for iron dextran completed their infusion schedules than those with more doses, but the opposite was seen for iron sucrose. We assessed the impact of the national shortage of iron dextran examining infusion reactions with various iron infusions and doses.

Surge in Eye Drop Safety Concerns and Interest in Alternative Dry Eye Disease Therapy Following Eye Drop Recalls: A Cross-Sectional Google Trends Analysis.

Beginning in January 2023, numerous eye drops were recalled following reports of contamination. To investigate hesitancy in topical therapies for dry eye disease (DED), we analyzed trends in Internet search traffic for alternative DED therapies and eye drop safety concerns following initial recalls. Google Trends (GT) was used to measure the popularity of specific search terms during a given time period. The main GT output metric for gauging interest in a search term is the Search Volume Index (SVI). We collected worldwide SVI data for terms "dry eye vitamin," "are eye drops safe," "stop eye drops," "lipiflow," "ilux treatment," "dry eye mask," "dry eye warm compress," "omega-3 for dry eyes," "dry eye plugs," "dry eye humidifier," "itear," and "IPL dry eye" from April 24, 2022, to October 29, 2023. Statistical analysis was performed with Microsoft Excel v.16.77.1, and comparisons between groups were performed using paired t tests. A significant increase in SVI was observed for most keywords. When comparing the 40-week period before and after the initial recall, 7/10 alternative DED therapies demonstrated a statistically significant surge in Internet search traffic after recall (P < 0.05). Furthermore, 2/2 keywords pertaining to eye drop safety concerns demonstrated an increase in SVI (P < 0.0001). We identified a significant surge in Internet search activity for eye drop safety and alternative DED therapies following eye drop recalls. Public health agencies and physicians may find this information valuable while attempting to address safety concerns and navigating noncompliance of routine eye drop therapy.

Management of Pulmonary Mucormycosis: A Systematic Review

Background Mucormycosis is a life-threatening fungal infection. Rhino-orbito-cerebral mucormycosis (ROCM) and pulmonary mucormycosis (PM) are the most common presentations. This systematic review focuses on the management of PM. Although the mortality from PM has improved over the last few decades, it is still high, at 49.8% (Muthu, Agarwal, et al., 2021). Objective The objective is to identify and map the management of PM. Design This review is designed for knowledge synthesis, with a systematic approach to identifying, synthesizing, and mapping treatment protocols for the management of PM. Methods This systematic review provides a clear, reproducible methodology. It is reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Inclusion criteria were defined: peer-reviewed journal articles published in English from 2018 to 2023 relating to treatment protocols for PM, where the full text of the article was available. Exclusion criteria were also defined - articles that focus on limited treatment regimens, such as the use of amphotericin B only, or topics not relevant to the research question, such as fungal infections and pulmonary diseases unrelated to mucormycosis. Results The results span six years, from 2018 to 2023, with 355 articles identified. After removing duplicates, 227 papers remained. Inclusion and exclusion criteria were applied, with 202 articles excluded as a result. The remaining 19 articles were deemed relevant. In addition, seven relevant articles were identified via citation tracking and two articles identified by hand search. Thus, a total of 28 articles thus reviewed. The management of PM was mapped in tabular and diagrammatic form. Conclusion The results indicate that early diagnosis, early and aggressive surgery, and effective antifungals may improve survival. There is a shift away from using Am-B and a clear preference for L-AmB as a first-line antifungal. Posaconazole and Isavuconazole are the drugs of choice for stepdown, maintenance, and salvage therapy, and as alternative therapies. The control of co-morbidities is a crucial aspect of treatment. Cytokines and hyperbaric oxygen may be beneficial. The therapeutic value of iron chelators, zinc, and nebulized amphotericin B (NAB) merit further study.

Investigating the effects of co-supplementation with alpha-linolenic acid and L-carnitine on inflammatory status, oxidative stress, clinical symptoms, mental health and quality of life in women with migraine: a protocol for a randomized, triple-blind, placebo-controlled trial

BackgroundMigraine is a severe neurological disorder that is recognized as one of the most common debilitating diseases worldwide. Although the exact cause of migraine is not known, research suggests that inflammation, oxidative stress, mitochondrial dysfunction, and insufficient nutrients may contribute to its development. Studies indicate that nutrition-based approaches are safer and more cost-effective strategies for managing migraine symptoms compared to medication. In this regard, the impact of nutrition, as a complementary medicine, is largely attributed to that of certain nutrients on inflammation and mitochondrial function. It is hypothesized that alpha-linolenic acid and L-carnitine, which possess anti-inflammatory and antioxidant properties, may be synergically beneficial for migraine patients. Therefore, this study will be conducted to assess the efficacy of alpha-linolenic acid and L-carnitine co-supplementation in patients with migraine.MethodsThis is a parallel, randomized, triple-blind, placebo-controlled clinical trial, in which 80 women aged 20 to 50 years with migraine will be assigned to receive either intervention group (n = 40) receiving both 1000 mg/day flaxseed oil and 500 mg/day L-carnitine simultaneously for 12 weeks, or control group (n = 40) receiving both 1000 mg/day paraffin oil and 500 mg/day maltodextrin as the placebos for the same duration. The primary outcomes include changes in clinical symptoms of migraine, including frequency, severity, and duration of attacks, serum levels of C–reactive protein (CRP), total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD). Secondary outcomes include mental health, sleep quality, and quality of life (QOL).DiscussionIn this study, we aim to investigate the potential benefits of combining alpha-linolenic acid and L-carnitine as a treatment option for migraine sufferers. Migraine, characterized by recurrent severe headaches, affects a significant portion of the population and can significantly impact an individual's quality of life. By studying alternative therapies such as alpha-linolenic acid and L-carnitine, researchers hope to expand the range of treatment options available and potentially provide relief to migraine sufferers.Trial registrationIranian Registry of Clinical Trials (www.irct.ir) (ID: IRCT20121216011763N57). Registration date: 29 March 2023.Trial statusThe protocol is version 1.0 dated December 30, 2023. Recruitment began on July 10, 2023, and is expected to be completed by January 22, 2024.

Evaluating the Anti-Osteoporotic Potential of Mediterranean Medicinal Plants: A Review of Current Evidence.

Background: Bones are biological reservoirs for minerals and cells, offering protection to the other organs and contributing to the structural form of the body. Osteoporosis is a prevalent bone condition that significantly impacts people's quality of life. Treatments utilizing natural products and medicinal plants have gained important attention in the management of osteoporosis and its associated implications, such as osteoporotic fractures. Even though thousands of plants grow in the Mediterranean region, the use of medicinal plants as an alternative therapy for osteoporosis is still limited. Methods: This article provides a comprehensive overview of seven Mediterranean medicinal plants that are used in osteoporosis and osteoporotic fractures in in vitro, in vivo, and clinical trials. The mechanism of action of the medicinal plants and their bioactive compounds against diseases are also briefly discussed. Results: The findings clearly indicate the ability of the seven medicinal plants (Ammi majus, Brassica oleracea, Ceratonia siliqua L., Foeniculum vulgare, Glycyrrhiza glabra, Salvia officinalis, and Silybum marianum) as anti-osteoporosis agents. Xanthotoxin, polyphenols, liquiritin, formononetin, silymarin, and silibinin/silybin were the main bioactive compounds that contributed to the action against osteoporosis and osteoporotic fractures. Conclusions: In this review, the Mediterranean medicinal plants prove their ability as an alternative agent for osteoporosis and osteoporotic fractures instead of conventional synthetic therapies. Thus, this can encourage researchers to delve deeper into this field and develop medicinal-plant-based drugs.

Safety and efficacy of oxycodone for refractory dyspnea in end-stage heart failure patients with chronic kidney disease: a case series of eight patients

BackgroundMorphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease. MethodsThis single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events.ResultsOxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% (n = 6) and ≥ 50% (n = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m2. The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5–10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment.ConclusionsThis study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine.

A Holistic View on Erectile Dysfunction: South African Medicinal Plants as Sustainable Alternative Therapies

Erectile dysfunction is a common problem affecting men worldwide, especially as they age. This condition is characterized by the inability to achieve or maintain an erection firm enough for sexual intercourse and may result from various factors, including vascular, neurogenic, hormonal, and psychological. Common first-line treatment options for the disease have relied on phosphodiesterase-5 inhibitors such as sildenafil (Viagra), which are costly, inaccessible, and sometimes result in adverse health effects. Consequently, there has been increasing interest in exploring medicinal plants as alternative remedies because of their easy access and affordability. In South Africa, 75 plant species with properties that affect testosterone levels, luteinizing hormone, and follicle-stimulating hormone are used as aphrodisiacs. Some plant extracts can increase blood testosterone concentrations and stimulate penile erection by maintaining nitric oxide levels. This paper presents current information about the possible utilization of South African medicinal plants as viable and readily available therapeutic alternatives for managing erectile dysfunction. In addition, it discusses in detail the various mechanisms of action of medicinal plants in managing the disease. The information on the efficacy of African medicinal plants in managing erectile dysfunction provided in this review will help increase awareness of the sustainable use of natural products. It may serve as a basis for including indigenous herbal remedies in the guidelines for erectile dysfunction management as potential treatment options in Africa.

Protective effect and mechanism of rapamycin on pulmonary fibrosis induced by Chlormethine in mice

To evaluate the therapeutic effect and mechanism of rapamycin (RAPA) on pulmonary fibrosis induced by chlormethine in C57BL/6N mice. Based on body weight, the 18-20 g C57BL/6N mice were randomly divided into five groups: control group, chlormethine group, chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, with ten mice in each group. Mice were put to death on the 21st day after the first administration of chlormethine. HE staining and Masson staining were used to observe the pathological changes and degree of fibrosis in the lung tissue of mice, and RT-PCR was used to detect collagen Ⅰ, E-cadherin, vimentin, and α-SMA mRNA expression. After 21 days of administration of chlormethine to mice, significant pulmonary fibrosis characteristics were observed in the lung tissue of the mice. Compared with the chlormethine group, the weight of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, significantly increased (P<0.05). Compared with the chlormethine group, the expression of pulmonary fibrosis-related indicators (collagen Ⅰ, E-cadherin, vimentin, and α-SMA) significantly improved (P<0.05) in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group. Compared with the chlormethine group, the pathological changes and collagen deposition in the lung tissue of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, were significantly improved. Transcriptome analysis of the lung tissue of mice revealed that RAPA treatment of chlormethine-induced pulmonary fibrosis might be related to NF-kappa B signaling pathway. Compared with the chlormethine group, the mRNA expression of p65 in the lung tissue of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, significantly decreased (P<0.01). RAPA has a protective effect on pulmonary fibrosis induced by chlormethine in mice. Its efficacy is comparable to that of dexamethasone, which is currently being used in clinical practice. It is a new alternative therapy, and its mechanism may be related to inhibiting the activation of the NF-kappa B signaling pathway.

Antiurolithic activity of Zaleya pentandra (L.) C Jeffrey in ethylene glycol-induced calcium oxalate crystal rat model; A scientific validation of traditional use for kidney stone prevention

Ethnopharmacological relevanceTraditional herbal remedies have been used for treating nephrolithiasis, but the relevant scientific evidence is limited. Zaleya pentandra (L.) C. Jeffrey is traditionally used for the prevention of kidney stones in various cultures. However, its efficacy has not been scientifically studied. Aim of the studyThis study aimed to investigate the antiurolithic activity of Zaleya pentandra, and validate its traditional used for preventing kidney stones. Materials and methodsThe crude ethanolic extract of Z. pentandra (Zp.Crd) was evaluated through in vitro and in vivo studies. In vitro experiments assessed its impact on crystal count and morphology in metastable calcium oxalate solutions. In vivo studies involved diuretic and ethylene glycol-induced calcium oxalate crystal formation in male Wistar rats. ResultsZp.Crd transforms calcium oxalate crystals from harmful calcium oxalate monohydrate (COM) to calcium oxalate dihydrate (COD). In vivo, Zp.Crd exhibited dose-dependent (30–300 mg/kg) diuretic activity in rats by significantly increasing urinary sodium (Na+) and potassium (K+) excretion, similar to the standard diuretic hydrochlorothiazide (HCT). In the urolithiasis model, Zp.Crd exhibited dose-dependent antiurolithic effects by reducing kidney crystals and significantly altering lithogenic factors induced by ethylene glycol, including crystalluria, oxaluria, calcium, creatinine, and urea, in the urine and serum of treated rats. Zp.Crd also exhibited antioxidant effects, effectively combating oxidative lithogenic stress in rats. ConclusionZp.Crd has been shown to demonstrate antiurolithic activity against CaOx stones through CaOx crystal inhibition, diuretic activity, antioxidant properties, hypocalciuric effects, and hypercitrauric actions. The findings underscore Zp.Crd's potential as a viable alternative or supplemental therapy to current urolithiasis treatments, paving the door for further clinical trials and its inclusion into modern medical practices.

7038 Continuous Subcutaneous Hydrocortisone Infusion Is Practical And Effective In Select Patients With Adrenal Insufficiency

Abstract Disclosure: J.E. Lee: None. O. Hamidi: None. S. Mirfakhraee: None. Continuous subcutaneous hydrocortisone infusion (CSHI) via insulin pump is an alternative therapy for treating patients with adrenal insufficiency (AI) and allows for adjustable hydrocortisone delivery to provide more physiologic glucocorticoid replacement. Retrospective case series of 9 patients on CSHI showed a reduction in total daily dose of glucocorticoid by 34% and a decrease in hospitalization admissions due to adrenal crisis by 50%. In a double-blind placebo-controlled study, CSHI in patients with primary AI did not demonstrate benefit in subjective health status metrics compared to oral hydrocortisone; however, patients had good baseline subjective health scores. Due to a scarcity of data, CSHI is likely underutilized in patients who may benefit from this individualized therapy. Our research objectives were to analyze the change in total daily glucocorticoid dose, number of adrenal crises events and hospitalization days, glucocorticoid-related comorbidities, and quality of life of patients transitioned to CSHI. We performed a single-center, retrospective longitudinal follow-up study in 23 consecutive patients (87% women, median age 40 years at time of CSHI initiation) treated with CSHI between 2015 and 2023. Types of adrenal insufficiency were 48% secondary AI, 35% glucocorticoid induced AI, and 17% primary AI. CSHI delivery settings were generated by a formula that we derived using each patient’s daily oral glucocorticoid dose and preferred waking time. Median time from AI diagnosis to CSHI implementation was 41 months, and median duration of CSHI was 25 months. Total daily dose of glucocorticoid (in hydrocortisone equivalent) before CSHI vs during CSHI decreased from 30.0mg (15.0mg to 80.0mg) to 26.6mg (14.4mg to 200.5mg) (p= 0.45). Median number of adrenal crisis events decreased from 1 (0 to 13) to 0 (0 to 38) (p=0.25), and hospitalization days due to adrenal crisis decreased from 2 (0 to 46) to 0 (0 to 58) (p=0.53). No significant differences were noted for change in weight, blood pressure, diabetes, cardiovascular and cerebrovascular events, total cholesterol, LDL, and triglyceride levels. Median HDL decreased from 59 to 51 (p=0.01). In terms of subjective health status, 10 patients completed SF-36 survey while on CSHI. Significant impairments were noted in physical health, vitality, and general health with median score less than 40. At the conclusion of the study, 20 patients (87%) preferred CSHI therapy. Only 3 patients stopped CSHI for reasons of inconvenience, skin irritation at pump site, and better symptom control on oral therapy. No significant CSHI-related safety concerns were noted. In conclusion, CSHI is a safe and effective way to deliver individualized therapy to patients with difficult to control AI. CSHI led to reduction in glucocorticoid exposure and fewer adrenal crisis events and hospitalization days due to adrenal crisis. Presentation: 6/1/2024

New strategies to enhance antimicrobial photo-sonodynamic therapy based on nanosensitizers against bacterial infections.

The rapid evolution and spread of multidrug resistance among bacterial pathogens has significantly outpaced the development of new antibiotics, underscoring the urgent need for alternative therapies. Antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy have emerged as promising treatments. Antimicrobial photodynamic therapy relies on the interaction between light and a photosensitizer to produce reactive oxygen species, which are highly cytotoxic to microorganisms, leading to their destruction without fostering resistance. Antimicrobial sonodynamic therapy, a novel variation, substitutes ultrasound for light to activate the sonosensitizers, expanding the therapeutic reach. To increase the efficiency of antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy, the combination of these two methods, known as antimicrobial photo-sonodynamic therapy, is currently being explored and considered a promising approach. Recent advances, particularly in the application of nanomaterials, have further enhanced the efficacy of these therapies. Nanosensitizers, due to their improved reactive oxygen species generation and targeted delivery, offer significant advantages in overcoming the limitations of conventional sensitizers. These breakthroughs provide new avenues for treating bacterial infections, especially multidrug-resistant strains and biofilm-associated infections. Continued research, including comprehensive clinical studies, is crucial to optimizing nanomaterial-based antimicrobial photo-sonodynamic therapy for clinical use, ensuring their effectiveness in real-world applications.

TMT-Based Quantitative Proteomics Revealed the Antibacterial Mechanism of Cinnamaldehyde against MRSA.

Natural plant extracts have demonstrated significant potential in alternative antibiotic therapies. Cinnamaldehyde (CA) has garnered considerable attention as a natural antibacterial agent. In this study, Tandem mass tag (TMT) quantitative proteomics combined with Western blot and RT-qPCR methods were employed to explore the antibacterial mechanism of CA against Methicillin-Resistant Staphylococcus aureus (MRSA) at the protein level. The results showed that a total of 254 differentially expressed proteins (DEPs) were identified in the control group and CA treatment group, of which 161 were significantly upregulated and 93 were significantly downregulated. DEPs related to nucleotide synthesis, homeostasis of the internal environment, and protein biosynthesis were significantly upregulated, while DEPs involved in the cell wall, cell membrane, and virulence factors were significantly downregulated. The results of GO and KEGG enrichment analyses demonstrated that CA could exert its antibacterial effects by influencing pyruvate metabolism, the tricarboxylic acid (TCA) cycle, teichoic acid biosynthesis, and the Staphylococcus aureus (S. aureus) infection pathway in MRSA. CA significantly inhibited the expression of recombinant protein MgrA (p < 0.05), significantly reduced the mRNA transcription levels of mgrA, hla, and sdrD genes (p < 0.05), and thermostability migration assays demonstrated that CA can directly interact with MgrA protein, thereby inhibiting its activity. These findings suggest that CA exerts its antibacterial mechanism by regulating the expression of related proteins, providing a theoretical basis for further development of clinical applications of antimicrobial agents derived from natural plant essential oils in the treatment of dairy cow mastitis.

Effectiveness of Azadirachta indica and Ocimum gratissimum for Acne Vulgaris: A Literature Review

Acne vulgaris is a common dermatological condition characterized by inflammation of the pilosebaceous units, predominantly affecting adolescents and young adults. Its multifactorial etiology involves hormonal imbalances, microbial overgrowth, and environmental factors, leading to increased sebum production and inflammation. Conventional treatments often vary in efficacy and tolerability, driving interest in alternative therapies to reduce the severity and recurrence of lesions and enhance appearance, the acne severity. This literature review explores the therapeutic potential of two herbal remedies, Azadirachta indica (Neem) and Ocimum gratissimum (African basil), known for their antimicrobial, anti-inflammatory, and antioxidant properties. Azadirachta indica is recognized for its rich phytochemical profile, including compounds like nimbin and azadirachtin, which effectively combat acne pathogens such as Cutibacterium acnes. Meanwhile, Ocimum gratissimum exhibits significant antimicrobial and antioxidant activities, contributing to skin healing and sebum regulation. The combined use of these herbs offers a holistic approach to acne management, targeting multiple aspects of its pathogenesis, including inflammation and microbial imbalance. The therapeutic benefits of Azadirachta indica and Ocimum gratissimum highlight their valuable role in advancing dermatological care and offer promising prospects for individuals seeking holistic and plant-based solutions for acne management. This review emphasizes the potential and effectiveness of Azadirachta indica and Ocimum gratissimum in advancing dermatological care and providing effective, plant-based solutions for acne management. Keywords: Acne vulgaris, azadirachta indica, clove basil, neem, ocimum gratissimum, treatment

Real-world evaluation of CYP2C19 guided antiplatelet therapy in patients undergoing intracranial aneurysm repair.

Aim: To evaluate the feasibility and impact of using CYP2C19 genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting.Patients & methods: A single-center, retrospective, observational cohort study was conducted in 112 patients undergoing intracranial aneurysm repair with flow-diversion stenting from 2014 to2021. Data were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor or prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]).Results: In the study population, CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to the stent procedure and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared with NM/RM/UMs (57.1 vs. 8.5%, respectively, p<0.0001). The frequency of thromboembolic events over 12months did not significantly differ across clopidogrel-treated IM/PMs, clopidogrel-treated NM/RM/UMs and patients on alternative therapy (p=0.352); although, event numbers were low.Conclusion: A pre-emptive CYP2C19 genotyping strategy to guide antiplatelet therapy selection in intracranial aneurysm repair patients is feasible in a real-world clinical setting. Larger studies are needed to assess the impact on clinical outcomes.

Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study

BackgroundTreatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC.MethodsThis retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted.ResultsA total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5–13.1) and 5.4 (95% CI: 3.8–7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016).ConclusionLenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

Synergistic Effect Antibacterial Activity of The Combination of Andaliman (Zanthoxylum acanthopodium DC) Fruit Essential Oil and Erythromycin against Streptococcus mutans and Streptococcus pyogenes

Background: The concept of synergism is one of the approaches taken to combat the problems related to antibiotic resistance. Objectives: The goal of this study was to determine the synergistic effect of antibacterial activity of a combination of essential oil of Zanthoxylum acanthopodium DC fruit and erythromycin against Streptococcus mutans and Streptococcus pyogenes. Methods: The broth microdilution assay was used to determine the Minimum Inhibitory Concentration (MIC) of Z. acanthpodium DC fruit essential oil and erythromycin. The synergistic effects were assessed using the checkerboard method. Results: MIC value of Z. acanthopodium DC fruit essential oil against both bacteria was 2500 mg/mL. The combination of Z. acanthopodium DC fruit essential oil and erythromycin had a synergistic effect against S. mutans and S. pyogenes with fractional inhibitory concentration index (FICI) values of 0.375 and 0.0872, respectively. Conclusions: These results suggest that a combination of herbal plants and conventional antibiotics could be used as an alternative therapy for bacterial infections.