Establishment of high-performance liquid chromatography-photodiode array method for 43 weight loss agents and effect of basic environment on bisacodyl degradation.

RATIONALE: The demand for weight loss products is increasing as slimness emerges as the new aesthetic standard and people's desire to achieve it increases. In addition, the distribution and sale of products containing illegal ingredients, pharmaceuticals, and chemicals for which safety is not guaranteed and that cannot be used as foods or dietary supplements are increasing. Thus, the development of an analytical method that could monitor these illegal products is required. METHODS: A high-performance liquid chromatography-photodiode array method capable of rapid and reliable qualitative and quantitative analyses of 43 weight loss agents was established and validated. RESULTS: The process involved dividing analytes into three groups for rapid analysis; when bisacodyl was mixed with chlorocyclopentylsibutramine, it decomposed into its metabolites: monoacetyl bisacodyl and bis-(p-hydroxypheny)-pyridyl-2-methane. This decomposition was due to NaOH that was used to prepare the chlorocyclopentylsibutramine standard solution. Bisacodyl did not degrade when mixed with neutralized chlorocyclopentylsibutramine, whereas when NaOH was added, it rapidly degraded. We identified the bisacodyl degradation products using liquid chromatography-quadrupole-Orbitrap/mass spectrometry. MS2 spectra with proposed structures of fragment peaks were also obtained. CONCLUSIONS: The developed method could be used to regulate slimming products that threaten public health, and knowledge of bisacodyl degradation will be used as the basis for developing an analytic method.

Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord. Although the disease's pathophysiological mechanism remains poorly understood, multifactorial mechanisms affecting motor neuron loss converge to worsen the disease. Although two FDA-approved drugs, riluzole and edaravone, targeting excitotoxicity and oxidative stress, respectively, are available, their efficacies are limited to extending survival by only a few months. Here, we developed combinatorial drugs targeting multifactorial mechanisms underlying key components in ALS disease progression. Using data analysis based on the genetic information of patients with ALS-derived cells and pharmacogenomic data of the drugs, a combination of nebivolol and donepezil (nebivolol-donepezil) was identified for ALS therapy. Here, nebivolol-donepezil markedly reduced the levels of cytokines in the microglial cell line, inhibited nuclear factor-κB (NF-κB) nucleus translocation in the HeLa cell and substantially protected against excitotoxicity-induced neuronal loss by regulating the PI3K-Akt pathway. Nebivolol-donepezil significantly promoted the differentiation of neural progenitor cells (NPC) into motor neurons. Furthermore, we verified the low dose efficacy of nebivolol-donepezil on multiple indices corresponding to the quality of life of patients with ALS in vivo using SOD1G93A mice. Nebivolol-donepezil delayed motor function deterioration and halted motor neuronal loss in the spinal cord. Drug administration effectively suppressed muscle atrophy by mitigating the proportion of smaller myofibers and substantially reducing phospho-neurofilament heavy chain (pNF-H) levels in the serum, a promising ALS biomarker. High-dose nebivolol-donepezil significantly prolonged survival and delayed disease onset compared with vehicle-treated mice. These results indicate that the combination of nebivolol-donepezil efficiently prevents ALS disease progression, benefiting the patients' quality of life and life expectancy.

Intramuscular neural distribution of the obturator internus muscle regarding injective treatment.

INTRODUCTION: The obturator internus muscle is frequently targeted for injective treatments such as botulinum toxin injections in the management of pain syndromes. However, there are controversies over injective method delivering injection to the muscle. METHOD: A method called modified Sihler's method was used to stain the OI muscle in 16 specimens to reveal the intramuscular neural distribution of the muscle. RESULT: The greatest intramuscular neural distribution was located on the 2/10-4/10 of the muscle in the medial edge of the obturator foramen (0/0) to the greater trochanter of the femur (10/10). CONCLUSION: The result suggests that botulinum neurotoxin should be delivered in the intrapelvic portion of the obturator internus muscle. As most of the extrapelvic portion of the obturator muscle is composed of a tendinous portion, it should be considered unsuitable as an injection site by medical professionals.

A scoping review of the different types of exercise programs proposed for the improvement of postural balance in adolescents with idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), which is the most common type of scoliosis, is a progressive disease that occurs in children aged 10-16 years. Abnormal curvature in AIS provokes spinal asymmetry of the upper body alignment and might deteriorate postural balancing and control ability. OBJECTIVE: To evaluate the effect of exercise interventions on balance and postural stability in patients with adolescent idiopathic scoliosis. METHODS: Embase, Scopus, Pubmed (Medline) and Web of Science databases were searched using the terms idiopathic scoliosis, physiotherapy, and balance. The articles selected were published in English in peer-reviewed journals from 2012 to July 2022. RESULTS: Ten studies met the inclusion criteria. The PEDro scale values ranged from 2 to 6 (mean, 3.6), indicating a low level of scientific rigor. In the sample studies, spinal stabilization exercises were most often trialed (n= 3), followed by Schroth's exercise (n= 2), stretching and self-elongation exercise (n= 2), the exercise protocol of Blount and Moe, physiotherapeutic scoliosis-specific exercise, and proprioceptive neuromuscular facilitation exercise (all n= 1). CONCLUSIONS: Physical therapists will be able to apply hippotherapy, Schroth exercise, physiotherapy scoliosis-specific exercise, trunk stabilization, proprioceptive neuromuscular facilitation exercise, spinal stabilization exercise, core stabilization exercise, and body awareness therapy to manage balance impairments in patients with adolescent idiopathic scoliosis, and further studies are needed to provide stronger evidence.

Anatomical proposal of local anesthesia injection for median nerve block in treating hyperhidrosis with botulinum neurotoxin.

INTRODUCTION: Hyperhidrosis, causing excessive sweat, can be treated with Botulinum neurotoxin injection. Botulinum toxin, an effective and safe treatment for hyperhidrosis, unfortunately involves significant pain due to multiple injections. This study aims to propose a more efficient and less painful approach to nerve blocks for relief, by identifying optimal injection points to block the median nerve, thereby enhancing palmar hyperhidrosis treatment. METHODS: This study, involving 52 Korean cadaver arms (mean age 73.5 years), measured the location of the median nerve relative to the transverse line at the pisiform level to establish better nerve block injection sites. RESULTS: In between the extensor carpi radialis and palmaris longus, the median nerve was located at an average distance of 47.39 ± 6.43 mm and 29.39 ± 6.43 mm from the transverse line at the pisiform level. DISCUSSION: To minimize discomfort preceding the botulinum neurotoxin injection, we recommend the optimal injection site for local anesthesia to be located 4 cm distal to the transverse line of the pisiform, within the tendons of the palmaris longus and flexor carpi radialis muscles.

Intramuscular neural distribution of the teres minor muscle using Sihler's stain: application to botulinum neurotoxin injection.

The aim of this study was to elucidate the intramuscular arborization of the teres minor muslce for effective botulinum neurotoxin injection. Twelve specimens from 6 adult Korean cadavers (3 males and 3 females, age ranging from 66 to 78 years) were used in the study. The reference line between the 2/3 point of the axillary border of the scapula (0/5), where the muscle originates ant the insertion point of the greater tubercle of the humerus (5/5). The most intramuscular neural distribution was located on 1/5-3/5 of the muscle. The tendinous portion was observed in the 3/5-5/5. The result suggests the botulinum neurotoxin should be delivered in the 1/5-3/5 area of the teres minor muscle.

Exploring the Impact of Appetite Alteration on Self-Management and Malnutrition in Maintenance Hemodialysis Patients: A Mixed Methods Research Using the International Classification of Functioning, Disability and Health (ICF) Framework.

Hemodialysis (HD) patients face a common problem of malnutrition due to poor appetite. This study aims to verify the appetite alteration model for malnutrition in HD patients through quantitative data and the International Classification of Functioning, Disability, and Health (ICF) framework. This study uses the Mixed Method-Grounded Theory (MM-GT) method to explore various factors and processes affecting malnutrition in HD patients, create a suitable treatment model, and validate it systematically by combining qualitative and quantitative data and procedures. The demographics and medical histories of 14 patients were collected. Based on the theory, the research design is based on expansion and confirmation sequence. The usefulness and cut-off points of the creatinine index (CI) guidelines for malnutrition in HD patients were linked to significant categories of GT and the domain of ICF. The retrospective CIs for 3 months revealed patients with 3 different levels of appetite status at nutrition assessment and 2 levels of uremic removal. In the same way, different levels of dry mouth, functional support, self-efficacy, and self-management were analyzed. Poor appetite, degree of dryness, and degree of taste change negatively affected CI, while self-management, uremic removal, functional support, and self-efficacy positively affected CI. This study identified and validated the essential components of appetite alteration in HD patients. These MM-GT methods can guide the selection of outcome measurements and facilitate the perspective of a holistic approach to self-management and intervention.

Botulinum neurotoxin injection in the deltoid muscle: application to cosmetic shoulder contouring.

BACKGROUND AND OBJECTIVES: This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. METHODS: The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. RESULTS: The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. CONCLUSION: We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results.

Anatomical analysis of the motor endplate zones of the suprascapular nerve to the infraspinatus muscle and its clinical significance in managing pain disorder.

Myofascial pain syndrome caused by myofascial trigger points is a musculoskeletal disorder commonly encountered in clinical practice. The infraspinatus muscle is the region most frequently involved in the myofascial pain syndrome in the scapular region. The characteristics of the myofascial trigger points are that they can be found constantly in the motor endplate zone. However, localizing myofascial trigger points within the motor endplate zone and establishing an accurate injection site of the infraspinatus muscle has been challenging because the anatomical position of the motor endplate zone of the infraspinatus muscle is yet to be described. Therefore, this cadaveric study aimed to scrutinize the motor endplate zone of the infraspinatus muscle, propose potential myofascial trigger points within the muscle, and recommend therapeutic injection sites. Twenty specimens of the infraspinatus muscle for nerve staining and 10 fresh frozen cadavers for evaluation of the injection were used in this study. The number of nerve branches penetrating the infraspinatus muscle and their entry locations were analyzed and photographed. Modified Sihler's staining was performed to examine the motor endplate regions of the infraspinatus muscle. The nerve entry points were mostly observed in the center of the muscle belly. The motor endplate was distributed equally throughout the infraspinatus muscle, but the motor endplate zone was primarily identified in the B area, which is approximately 20-40% proximal to the infraspinatus muscle. The second-most common occurrence of the motor endplate zone was observed in the center of the muscle. These detailed anatomical data would be very helpful in predicting potential pain sites and establishing safe and effective injection treatment using botulinum neurotoxin, steroids, or lidocaine to alleviate the pain disorder of the infraspinatus muscle.

Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

Background: We have previously shown that the long non-coding (lnc)RNA prostate cancer associated 3 (PCA3; formerly prostate cancer antigen 3) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene PRUNE2 (a homolog of the Drosophila prune gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the PCA3/PRUNE2 regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression. Methods: The reciprocal PCA3 and PRUNE2 gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497). We compared the tumor gene expression of PCA3 and PRUNE2 to their corresponding expression in the normal prostate. We also serially examined clinical/pathological variables including time to disease recurrence. Results: We consistently observed increased expression of PCA3 and decreased expression of PRUNE2 in prostate cancer compared with the adjacent normal prostate across all tumor grades and stages. However, there was no association between the relative gene expression levels of PCA3 or PRUNE2 and time to disease recurrence, independent of tumor grades and stages. Conclusions: We concluded that upregulation of the lncRNA PCA3 and targeted downregulation of the protein-coding PRUNE2 gene in prostate cancer could be early (rather than late) molecular events in the progression of human prostate tumorigenesis but are not associated with biochemical recurrence. Further studies of PCA3/PRUNE2 dysregulation are warranted. Funding: We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).

Sonoanatomy and an ultrasound scanning protocol of the intramuscular innervation pattern of the infraspinatus muscle.

INTRODUCTION: Botulinum neurotoxin injection is a valuable treatment method for patients with myofascial pain syndrome in the infraspinatus muscle. However, there is no botulinum neurotoxin injection guideline, and the most appropriate injection site based on topographical anatomic information for this injection to effectively treat myofascial pain syndrome in the infraspinatus muscle is unclear. The purpose of this study was to evaluate the intramuscular nerve terminal of the infraspinatus muscle and to suggest the most efficient botulinum neurotoxin injection sites. METHODS: This study used 5 formalin-embalmed and 10 fresh frozen cadavers with a mean age of 78.9 years. Sihler's staining was applied to evaluate the intramuscular nerve terminal of the infraspinatus muscle. The ultrasound scanning of the infraspinatus muscle was performed based on the surface landmarks and internal structures near the scapular region. RESULTS: The intramuscular nerve terminal was mostly observed in the medial third area of the infraspinatus muscle. The deltoid tubercle, inferior angle, and acromion of the scapula are useful as surface landmarks to scan the infraspinatus muscle. DISCUSSION: The proposed injection sites based on the intramuscular nerve terminal and surface landmarks can be regarded as accurate locations to reach the cluster area of the intramuscular nerve terminal and each compartment of the infraspinatus muscle to manage the myofascial pain syndrome in the infraspinatus muscle.

Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.

Effectiveness of an integrative medicine approach to improve cognitive dysfunction and dementia: An observational study.

Despite the urgent need to control dementia, an effective treatment has yet to be developed. Along with the Korean government's policy of cooperation between conventional medicine (CM) and Korean medicine (KM), integrative medical services for dementia patients are being provided. This study aimed to compare the integrative medical clinic (IMC) for dementia used by Dongguk University Hospitals (DUH) with other service models and to review the characteristics and treatment outcomes of patients who had visited DUH over the past 5 years. Patients' electronic medical records from May 2015 to June 2020 were searched and their data were analyzed to evaluate the IMC's service model. Patient demographic and clinical characteristics, diagnostic tests, and treatment patterns for CM and KM were collected. The proportion of patients who did not show worsening cognitive function was described in detail. A strength of the DUH integrative medicine clinic is its ability to manage both KM and CM patients in the same space at the same time. Among the 82 patients who visited the clinic during our study period, 56 remained for data analysis after we excluded patients who met the exclusion criteria; nineteen patients had diagnoses of mild cognitive impairment. Among collaboration patterns, the first visit to the IMC had the highest proportion (55.4%). Among diagnosed tests in CM, laboratory tests and neuropsychological tests were used the most. In KM, a heart rate variability test was frequently used. The most common CM treatment prescribed was anticonvulsants, with 22 patients (39.2%) receiving donepezil, whereas the most frequent KM treatments were acupuncture (82.1%) and herbal medicine (78.6%). Twelve patients were followed up with the Mini-Mental State Examination, and 8 demonstrated either no worsening or improved cognition (baseline Mini-Mental State Examination range: 21-26). All 8 patients had mild cognitive impairment including 6 with amnestic, multidomain impairment. This study searched for a way to improve cognitive dysfunction and dementia using an integrative approach, and it shows promising results for mild cognitive impairment. However, more precisely designed follow-up studies are needed to address the present work's limitations of a retrospective study design and a small sample size.

Intercomparison study of fragmentation pathways and fragment ion structures for screening of illegal drugs and their novel analogues used to adulterate dietary supplements using liquid chromatography/quadrupole time-of-flight mass spectrometry.

RATIONALE: As public interest in health and immunity has increased in recent years, so has the demand for dietary supplements. However, supplements adulterated with illegal drugs and their novel analogues are being sold even as the pharmacological efficacies of these drugs are being advertised. Since the use of these illegal compounds can have serious side effects, they pose a risk to public health. Hence, in this study, we propose a strategy for proactively testing drugs and novel analogues that may be added to dietary supplements illegally. METHODS: The optimal conditions for liquid chromatography/quadrupole time-of-flight mass spectrometry were explored to determine the fragmentation patterns for 60 compounds. The optimal conditions were established by comparing the areas and heights of the precursor ion peaks at a fragmentor voltage of 125 or 175 V. Furthermore, the optimized spectra were acquired using collision energies of 1 to 50 eV. The energy value was selected based on the condition that the mass error of the precursor ions is 10 ppm or lower. RESULTS: The fragmentation pathway of each product ion and its chemical structure were predicted and determined. In addition, the obtained structural information was used to screen 18 seized samples. Based on the precursor ions and the corresponding fragmentation patterns, the unknown compounds present in the samples were identified as desulfonylchlorosildenafil and propoxyphenylthiohydroxy homosildenafil. CONCLUSIONS: We obtained mass spectrometry-based information for various compounds by predicting the fragmentation pathways and chemical structures of their fragment ions. Subsequently, based on the obtained structural information, we tested several seized samples and were able to detect two novel analogues in four of the samples. Therefore, the proposed approach is suitable for quickly and accurately identifying the unknown compounds detected in real-world samples.

Comprehensive Comparison of Chemical Composition and Antioxidant Activity of Panax ginseng Sprouts by Different Cultivation Systems in a Plant Factory.

In this study, the primary (such as amino acids, fatty acids, and minerals) and secondary (including ginsenosides, phenolic acids, and flavonols) metabolites and antioxidant effects of Panax ginseng sprouts (PGSs) by different cultivation systems, such as soil-substrate cultivation (SSC) and deep-water cultivation (DWC), in a plant factory has been observed. There was no significant difference in the total fatty acid (FA) contents. Particularly, the major FAs of PGSs were palmitic acid (207.4 mg/100 g) of saturated FAs and linoleic acid (397.6 mg/100 g) and α-linolenic acid (222.6 mg/100 g) of unsaturated FAs in the SSC system. The values of total amino acids were all higher in SSC than in DWC. In the case of ginsenosides, the total protopanaxtriol product was 30.88 mg/g in SSC, while the total protopanaxdiol product was 34.83 mg/g in DWC. In particular, the values of total phenolic acids and total flavonols were 133.36 and 388.19 ug/g, respectively, and SSC had a higher content than DWC. In conclusion, the SSC system was shown to be higher in nutritional constituents and antioxidant activities in soil cultivation, suggesting that PGS with SSC has a positive effect on the quality of PGS in a plant factory.

Guidance to trigger point injection for treating myofascial pain syndrome: Intramuscular neural distribution of the quadratus lumborum.

Postural habits and repetitive motion contribute toward the progress of myofascial pain by affecting overload on specific muscles, the quadratus lumborum (QL) muscle being the most frequently involved. The therapy of myofascial pain syndrome includes the release of myofascial pain syndrome using injective agents such as botulinum neurotoxin, lidocaine, steroids, and normal saline. However, an optimal injection point has not been established for the QL muscle. This study aimed to propose an optimal injection point for this muscle by studying its intramuscular neural distribution using the whole mount staining method. A modified Sihler's procedure was completed on 15 QL muscles to visualize the intramuscular arborization areas in terms of the inferior border of the 12th rib, the transverse processes of L1-L4, and the iliac crest. The intramuscular neural distribution of the QL had the densely arborized areas in the three lateral portions of L3-L4 and L4-L5 and the medial portion between L4 and L5.

Application of LC-MS/MS and UHPLC-Q-Orbitrap methods for determining 54 steroids in illegal dietary supplements and other sample types.

RATIONALE: With the development of the Internet and social network services, the public access to or use of illegal products has been increased via on/offline black markets. Steroids refer to the compounds yielding strong treatment effects on some diseases or muscle building, and are classified as the pharmaceutical compounds that are prohibited for personal use without a prescription. The prohibition is made for their potential risk to cause serious adverse effects along with their efficacies. METHODS: To monitor the distribution of illicit products containing steroids, a simple and reliable analytical method was established and validated, allowing rapid and simultaneous determination of 54 steroids in them. During the screening, LC-Q-Orbitrap/MS was performed first followed by quantitative analysis using LC-MS/MS. For the accurate and reliable analysis, the samples were extracted using QuEChERS to reduce the matrix effect. RESULTS: After the screening of 617 illegal samples advertised as being effective in alleviating various diseases or improving athletic performance with the established LC-Q-Orbitrap/MS method, the validated LC-MS/MS method was used to perform the quantitative analysis of the detected steroids. Of these, 142 samples were adulterated with steroids, and several samples with two or more steroids were detected. Due to the lack of previous studies on the toxicity of these illicit products, the side effects of consuming them are unpredictable and could be harmful. CONCLUSIONS: The development of LC-Q-Orbitrap/MS method accompanied by LC-MS/MS could be successfully applied to the inspection of illegal steroid products for public health, enabling the rapid and accurate detection of analytes and incorporation of non-analyte components.

Detection of 94 PDE-5is and Their Analogs Including N-Desmethylthiosildenafil in Various Formulations of Dietary Supplements and Food Samples Using HPLC and LC-Q-TOF/MS.

Consumption of foods and dietary supplements (DS) adulterated with unprescribed or non-permitted phosphodiesterase-5 inhibitors (PDE-5i) and their analogs can cause serious risk to human health. This study aims to analyze 93 PDE-5i and their analogs present in adulterated foods and DS using an established and validated method involving high-performance liquid chromatography (HPLC). The method was validated in solid and liquid samples, resulting in a limit of detection and quantitation of 0.03-0.5 and 0.08-1.6 µg/mL, respectively. Using the validated method, a total of 404 samples were screened. It was found that 32% of 404 samples were illegally adulterated with PDE-5i and their analogs; moreover, 16.9% of the adulterated samples were found to contain more than three compounds. HPLC-quadrupole-time-of-flight (TOF)/mass spectrometry (MS) analysis was conducted on all the samples to confirm the detected compounds accurately based on fragmentation ion patterns. In addition, sildenafil and tadalafil were detected from the capsule shells of DS unusually. Subsequently, the detected compounds were identified and quantified using HPLC at concentrations ranging from 0.007 to 370.0 mg/g. NMR analysis was carried out to confirm the accurate chemical structure of a compound found during the TOF/MS analysis, which did not match with the 93 reference standards.; it was identified to be N-desmethylthiosildenafil. In this study, various PDE-5i compounds and their analogs were detected from low to high concentrations in a sample. Therefore, the study sheds light on the misuse of PDE-5i and their analogs in consumable products, which pose a severe threat to public health.

Intramuscular Innervation of the Supraspinatus Muscle Assessed Using Sihler's Staining: Potential Application in Myofascial Pain Syndrome.

Despite the positive effects of botulinum neurotoxin (BoNT) injection into the neural arborized area, there is no anatomical evidence in the literature regarding the neural arborization of the supraspinatus muscle. The present study aimed to define the intramuscular neural arborized pattern of the supraspinatus muscle using the modified Sihler's staining method to facilitate the establishment of safe and effective injection sites in patients with myofascial pain in the supraspinatus muscle. Seventeen supraspinatus muscles from 15 embalmed cadavers were dissected. Precise suprascapular nerve entry locations were also observed. Intramuscular neural arborization was visualized by Sihler's staining. The supraspinatus muscle was divided into four portions named A, B, C, and D. The nerve entry points were observed in 88.2% (15 of 17 cases) of section B and 76.5% (13 of 17 cases) of section C of the supraspinatus muscle, respectively. The concentration of intramuscular neural arborization was highest in section B of the supraspinatus muscle, which was the center of the supraspinatus muscle. When the clinician performs a trigger point and a BoNT injection into the supraspinatus muscle, injection within the medial 25-75% of the supraspinatus muscle will lead to optimal results when using small amounts of BoNT and prevent undesirable paralysis.

Application of liquid chromatography-high resolution mass spectrometry and liquid chromatography-tandem mass spectrometry methods to 45 weight loss compounds in health functional food, food, and illegal drug.

In order to effectively and quickly monitor such illegal food and drugs, simultaneous screening and quantitative analysis for multiple compounds are needed. In this study, we established a method of identifying fragmentation ions of 45 compounds for weight loss using liquid chromatography and high-resolution mass spectrometry and developed a quantitation method through liquid chromatography and tandem mass spectrometry. Note that, 656 samples selected as health functional food, food, and illegal drug were applied. The detection rate of banned weight loss compounds in health functional food, food, and illegal drug was showed as 19.2, 27.3, 40.7%, respectively. Among them, sibutramine, sennoside A and B, ephedrine were most frequently detected in 237 samples that contained weight loss compounds. The detection range about sibutramine was 0.03-159.3 mg/g, sennoside was 0.1-97.6 mg/g, and ephedrine was 0.1-587.7 mg/g in the detected 237 samples. In addition, the unknown compounds not included in our simultaneous analysis method in some samples were identified as furosemide and chlorpheniramine. High selectivity of high resolution mass spectrometry combined with these fragmentation pathways and tandem mass spectrometry methods can be successfully applied to screening and identifying 45 weight loss compounds for continuous blocking and supervision of illegally distributed health functional food, food, and illegal drug.