Combined antiallodynic effects of Neurotropin®-tramadol and Neurotropin®-mirogabalin in rats with L5-spinal nerve ligation.

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50-200 NU/kg, p.o.), tramadol (7.5-60 mg/kg, p.o.), and mirogabalin (3-30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100-400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30-100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100-400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10-100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin-tramadol or Neurotropin-mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Predictors and associated factors with adverse drug reaction in people with epilepsy.

OBJECTIVES: There is a need for early identification and intervention of Adverse Drug Reaction (ADR) to alleviate the unacceptably growing burden, morbidity, and mortality associated with People With Epilepsy (PWE). This study is aimed at identifying associated factors and predictors of ADR among PWE. METHODS: It is an interviewer-administered questionnaire-based study consisting of 940 consenting participants aged 16 years and above attending epilepsy clinics for 5 years with diagnosis confirmed by International League against Epilepsy (ILAE) criteria and supported by Electroencephalography (EEG). Twenty-one-item Liverpool Adverse Effect Profile (LAEP) and 8-item Morinsky Medication Adherence Scale (MMAS) were used to assess ADR and adherence respectively. RESULTS: The highest reported ADR in PWE were nervousness (34.3%), aggression (33.6%), and weight gain (32.3%). Specifically, 20.1% of the participants complained of memory problems. On the other hand, ADR associated with skin, mouth/gum and hair loss was 9.3%, 8.9%, and 7.2% respectively, and these were the lowest reported ADRs. Using the MMAS, 545(90.2%), 28(4.6%), and 31(5.1%) of PWE in this study were classified as having high, medium, and low adherence, respectively. Duration of Anti-Seizure Medication (ASM) use and duration of epilepsy were the major determinants of ADR in PWE on the regression model. CONCLUSION: Duration of ASM use and duration of epilepsy are the major determinants of ADR in PWE. Effective strategies to identify and reduce ADR should be incorporated into the management of PWE by Health Care Providers (HCPs) to improve their quality of life.

Review on personal protective equipment: Emerging concerns in micro(nano)plastic pollution and strategies for addressing environmental challenges.

The COVID-19 pandemic was caused by the SARS-CoV-2 virus, marking one of the most catastrophic global health crises of the 21st century. Throughout this period, widespread use and improper disposal of personal protective equipment (PPE) emerged as a pressing environmental issue, significantly impacting various life forms. During the COVID-19 pandemic, there was a high rate of PEP disposal. An alarming 1.6 × 106 tons of plastic waste each day has been generated since the onset of the outbreak, predominantly from the inadequate disposal of PPE. The mismanagement and subsequent degradation of discarded PPE significantly contribute to increased non-biodegradable micro(nano)plastic (MNP) waste. This pollution has had profound adverse effects on terrestrial, marine, and aquatic ecosystems, which have been extensively of concern recently. Accumulated MNPs within aquatic organisms could serve as a potential route for human exposure when consuming seafood. This review presents a novel aspect concerning the pollution caused by MNPs, particularly remarking on their role during the pandemic and their detrimental effects on human health. These microplastic particles, through the process of fragmentation, transform into nanoparticles, persisting in the environment and posing potential hazards. The prevalence of MNP from PPE, notably masks, raises concerns about their plausible health risks, warranting global attention and comprehensive exploration. Conducting a comprehensive evaluation of the long-term effects of these processes and implementing effective management strategies is essential.

Factors associated with thermal injury of abdominal skin in focused ultrasound ablation of uterine fibroids.

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS). METHOD: A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal-Wallis H. RESULTS: (1) Abdominal scars (p = .007, OR = 2.187, 95% CI: 1.242-3.849), abdominal wall thickness (p < .001, OR = 1.042, 95% CI: 1.019-1.067), fundus fibroids (p = .038, OR = 1.790, 95% CI: 1.033-3.100), UFs with hyperintense/mixed T2-weighted imaging (T2WI) signals (p = .022, OR = 1.843, 95% CI: 1.091-3.115), average sonication power (AP) (p = .025, OR = 1.021, 95% CI: 1.003-1.039), and treatment time (TT) (p < .001, OR = 1.017, 95% CI: 1.011-1.023) were independent risk factors for thermal injury, while treatment volume (TV) (p = .002, OR = 0.775, 95% CI: 0.661-0.909) was a protective factor for injury. (2) Four groups were subdivided according to the degree of thermal injury(Group A: without skin injury. Group B: with changed T2WI signal in the abdominal wall, Group C: mild skin injury, Group D: severe skin injury), comparison of each with every other showed that the abdominal wall in Groups A and D was thinner than Groups B and C, with statistically significant differences (PAB<0.05, PAC<0.01, PDC<0.05, PDB<0.05); Group A was slightly thicker than D, however, without statistical difference. The ratio of sonication time (ST) to TV in Group A was the lowest of all (PAB, PAC, PAD all < 0.05). And as the level of thermal injury rose, the ratio gradually increased, however, without statistical difference. CONCLUSIONS: Based on our limited results, the following conclusion was made. (1) Abdominal scars, abdominal wall thickness, fundus fibroids, UFs with T2WI hyperintense/mixed signals, AP and TT were independent risk factor. (2) Neither too thick nor too thin abdominal walls would be recommended, as both might increase the risk of skin injury. (3) Noticeably, the risk of skin injury might increase considerably when the ST was longer and the sonication area was more fixed.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Baclofen in the treatment of alcohol use disorder: tailored doses matter.

AIMS: To address the question of tailored baclofen prescribing in alcohol use disorder (AUD) in relation to dose-dependent efficacy and the potential danger of high doses and to provide suggestions for the use of high doses of baclofen in the treatment of AUD. The context is the approvement in France of baclofen in the treatment of AUD without dose limitation, making French physicians, who usually prescribe baclofen in a tailored manner, often use high or very high doses. METHODS: A narrative review of the results of randomized controlled trials (RCTs) and observational studies that used tailored baclofen prescribing and of the severe adverse effects of baclofen that have been reported in the literature. RESULTS: The results show that RCTs using tailored doses of baclofen in AUD are not completely demonstrative, though they are encouraging according to certain meta-analyses, while observational studies that used tailored doses constantly show a good effectiveness of baclofen treatment. The results suggest that many severe adverse effects of baclofen could be related to a nonrespect by physicians of prescription rules and appropriate treatment monitoring. CONCLUSIONS: The use of tailored doses shows that the dose required to suppress cravings is highly variable, low or high, depending on each case. Analysis of the circumstances in which severe adverse effects occur suggest that a careful monitoring of baclofen prescribing might prevent a large majority of severe adverse effects. We propose that the education of the patients and the prescription skills, seriousness, and availability of the prescribing physicians are of major importance in the managing of tailored baclofen treatment of AUD.

Motoric Cognitive Risk Syndrome as a Predictor of Adverse Health Outcomes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD), and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aimed to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from ten electronic databases. The Newcastle-Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR = 2.02; 95% CI = 1.94-2.11), cognitive impairment (adjusted RR = 1.72; 95% CI = 1.49-1.99), falls (adjusted RR = 1.32; 95% CI = 1.17-1.50), mortality (adjusted RR = 1.66; 95% CI = 1.32-2.10), and hospitalization (adjusted RR = 1.46; 95% CI = 1.16-1.84); MCR had more prominent predictive efficacy for AD (adjusted RR = 2.23; 95% CI = 1.81-2.76) compared to VaD (adjusted RR = 3.78; 95% CI = 0.49-28.95), while excluding analyses from the study that utilized the timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (hazard ratios [HR] = 1.69; 95% CI = 1.08-2.02) and frailty (OR = 5.53; 95% CI = 1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR = 1.22; 95% CI = 1.11-1.34 vs. adjusted RR = 1.19; 95% CI = 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes, and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis and provide evidence to support future targeted interventions.

Evaluation of the pharmacokinetics of liposomal amphotericin B and analysis of the relationship between pharmacokinetics, efficacy and safety in patients with hematological diseases.

INTRODUCTION: This study aimed to identify factors responsible for changes in blood concentrations of a liposomal formulation of amphotericin B (AMPH-B, L-AMB) and analyze the relationships between blood concentrations and efficacy or toxicity. METHODS: L-AMB was administered to 30 patients being treated for hematological diseases. AMPH-B plasma concentrations were determined right before the initiation (Cmin) and at the end (Cmax) of infusion on at least 1 day, beginning on Day 3 of L-AMB treatment. The relationships of Cmin divided by dose (C/D ratio) to body weight, age, hepatic function, renal function, serum albumin, C-reactive protein (CRP), response, hypokalemia, and renal impairment were evaluated. RESULTS: C/D ratio was not correlated with age, hepatic function, renal function, or serum albumin. Body weight adjusted C/D ratio was negatively correlated with CRP. Cmax and Cmin were compared between responders and non-responders, those with or without hypokalemia, and those with or without renal impairment. A higher Cmax in patients with hypokalemia was the only significant difference seen. CONCLUSIONS: The negative correlation between CRP and plasma concentrations was likely caused by higher distribution of L-AMB from the blood to infected tissue in patients with a greater degree of infection, with a resulting decrease in plasma concentrations. AMPH-B plasma concentrations were not related to response. Higher Cmax of AMPH-B were observed in patients with hypokalemia, but no relationship between plasma concentration and renal toxicity was observed, suggesting that AMPH-B plasma concentrations appear to be minimally related to PD when used as L-AMB.

Disturbance of consciousness caused by dyclonine hydrochloride mucilage: a case report.

BACKGROUND: Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to endoscopic examinations such as electronic gastroscopy, and few adverse reactions have been reported. This article describes a patient who experienced a transient but severe disturbance of consciousness following oral dyclonine hydrochloride mucilage administration. CASE PRESENTATION: A 75-year-old female presenting with gastrointestinal bleeding was examined by electronic gastroscopy. Six minutes after oral dyclonine hydrochloride mucilage administration, the patient entered a comatose-like state accompanied by loss of limb muscle tone and profuse perspiration. This response was not accompanied by changes in cardiac rhythm, blood pressure, or respiration rate, suggesting an effect on higher brain centres. After ten minutes, the patient's symptoms were alleviated. CONCLUSION: We suggest that sites of dyclonine hydrochloride mucilage use be equipped with appropriate rescue devices for these rare events.

Comparing Efficacies of Different Exercises on Androgen Deprivation Therapy Adverse Effects in Prostate Cancer Patients: A Network Meta-Analysis.

INTRODUCTION: Previous studies showed exercise have efficacies for androgen deprivation therapy (ADT) adverse effects. To compare the efficacies of different exercises on ADT adverse effects, we conducted the network meta-analysis (NMA). METHODS: Literature retrieval was performed in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Nineteen studies (1,184 participants) were included. All analyses were performed in R 4.1.2 or RevMan 5.4.1. RESULTS: NMA results showed that compared with the control group, both aerobic + resistance training (ART) (MD = 5.92, 95% CI: 0.38; 11.46) and resistance exercise (RE) (MD = 5.62, 95% CI: 2.70; 8.55) improved quality of life (QoL). ART (P score: 0.72) may have superiority over RE (P score: 0.7). ART (MD = -10.89, 95% CI: -17.67; -4.11) significantly improved the performance of 400-m test. RE could significantly improve leg strength (MD = 118, 95% CI: 78.75; 157.25) and chest strength (MD = 13.30, 95% CI: 4.07; 22.53). RE ranked first for strength improvements of leg and chest. CONCLUSION: ART showed better efficacy for the QoL and significantly improved the performance of 400-m test. RE might be superior for the strengths of leg and chest. ART may be appropriate for patients with less significant muscle strength decline but also other adverse effects of ADT, such as decreased cardiopulmonary function.

Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma.

The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.

Study on the acute and subchronic oral toxicity of Calculus Bovis Sativus in rats.

This study aims to assess the acute and subchronic toxicity of Calculus Bovis Sativus (CBS), which is an ideal substitute for natural Calculus Bovis. After conducting a test of acute toxicity with KM mice of both sexes, it was determined that oral CBS had a lethal dosage (LD50) of greater than 9.26 g/kg BW. For ninety days, Wistar rats were fed on CBS orally at dosages of 0, 167, 501, and 1503 mg/kg BW/day, respectively, as part of the subchronic investigation. A comparison of the controls with the 1503 mg/kg and 501 mg/kg dosage groups revealed significant differences in the hematological and serum biochemical parameters, such as RBC, HGB, MONO%, PLT, LYMPH% and GLU, TP, ALB, and Ca2+, were observed. However, values of the above parameters fell within our laboratory's normal range. In terms of body weight, food intake, urinalysis, clinical chemistry, and pathology, no other adverse effects were observed. After 90 days of exposure, the no observed adverse effect level (NOAEL) of CBS in rats was determined to be 1503 mg/kg BW/day.

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Preclinical Safety Evaluation of the Human-Identical Milk Oligosaccharide Lacto-N-Triose II.

Lacto-N-triose II (LNT II), an essential human milk oligosaccharide and precursor to lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), was evaluated for safety. Genotoxicity was assessed through in vitro tests including Bacterial Reverse Mutation Test and mammalian cell micronucleus test, and a subchronic oral gavage toxicity study was conducted on juvenile Sprague-Dawley rats. In this study, LNT II was administered at dose levels of 0, 1,500, 2,500, or 5,000 mg/kg body weight (bw)/day for 90 days, followed by a 4-week treatment-free recovery period. LNT II was non-genotoxic in the in vitro assays. No compound-related effects were observed across all dosage levels based on various measures, including clinical observations, body weight gain, feed consumption, clinical pathology, organ weights, and histopathology. Consequently, the highest dosage of 5,000 mg/kg bw/day was established as the no-observed-adverse-effect-level (NOAEL). These results suggest the safe use of LNT II in young children formula and as a food ingredient, within the limits found naturally in human breast milk.

Allergic contact dermatitis to lip care cosmetic products - a systematic review.

Aim: Lip care cosmetics products are any external preparation used by people to prevent drying, chapping, dullness, and beautification of lips. This study aimed to review the literature on allergic reactions induced by different types of lip care cosmetic products. Methods: A literature search was performed in PubMed from inception to June 2022. The study included articles published in English and available in full text. References of illegible articles were searched. Studies describing any patient who developed allergic contact dermatitis after the application of lip care cosmetic products were included. Results: A total of 47 reports consisting of 58 individuals experienced allergic reactions to lip care products. Several lip care cosmetics products, such as lipsticks, lip balms, lip salve, lip gloss, lip liner, and lip plumper, were found to be associated with allergic reactions. The most common ingredients that caused the allergic contact dermatitis were castor oil, benzophenone-3, gallate, wax, and colophony. Conclusions: Lip care cosmetics products contain several components that have been associated with allergic reactions. Awareness needs to be created among the general public and dermatologists regarding the presence of possible allergens in lip care cosmetic products.

Subjective biosafety assessment of bisdemethoxycurcumin from the rhizomes of Curcuma longa.

Introduction/Background: Curcuma longa, a plant native to the Indian subcontinent has a variety of biological activities. Curcumin is the most abundant and biologically active compound with many therapeutic properties. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) - the two other bioactive components present in Curcuma longa, besides curcumin, are collectively termed curcuminoids. Apart from the well-known curcumin, BDMC also has been reported to possess promising biological and pharmacological effects, but very little scientific evidence on its safety assessment has been published.Objective: The present study was undertaken to determine the safety of pure BDMC from Curcuma longa extract in rodents which comprises of general toxicity (both four weeks and three months duration), reproductive/developmental toxicity and genotoxicity studies.Methods: The Good Laboratory Practice studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development.Results: No treatment-related adverse findings were seen in general toxicity testing and a no observed adverse effect level (NOAEL) of 1000 mg/kg/day was established after four weeks (sub-acute) and three-months (sub-chronic) dosing. Evaluation of fertility, embryo-fetal, and post-natal reproductive and developmental parameters also showed no adverse findings with a NOAEL of 1000 mg/kg/day established. The results of genotoxicity as evaluated by in vitro reverse mutation assay, and in vivo micronucleus test in mice indicate that BDMC did not induce any genotoxic effects.Conclusion: Oral administration of BDMC is safe in rodents and non-mutagenic, with no adverse effects under experimental conditions.

Endocrine Fever.

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

How I Follow Hodgkin Lymphoma in First Complete (Metabolic) Remission?

Hodgkin lymphoma is characterized by a high cure rate in the modern era of medicine regardless of stage, but patients suffer from a high risk of comorbidity associated with the administered therapy. The main aim of this review article is to assess and analyze the various comorbidities associated with Hodgkin lymphoma and address the survivorship of patients, including fertility, secondary cancers due to cardiovascular toxicity, and quality of life. Furthermore, this review explores the optimal strategy for detecting relapse. The treatment paradigm of Hodgkin lymphoma has shifted, with a paradigm shift toward achieving a high cure rate and low toxicity as a standard of care in this patient population. Checkpoint inhibitors, especially nivolumab, in combination with chemotherapy are increasingly being studied in the first line of therapy. However, their long-term toxicity remains to be assessed in longer follow-up. In conclusion, Hodgkin lymphoma survivors, regardless of their treatment, should be followed up individually by a multidisciplinary survivorship team in order to detect and properly treat the long-term side effects of therapy.

Investigation of the constituents of commercially available toothpastes.

OBJECTIVES: Toothpaste plays a pivotal role in oral and dental hygiene. This cross-sectional study not only investigates the constituents of toothpastes available in the market and their frequency across different brands but also delves into the potential side effects, irritations, or unfavourable outcomes of these constituents, emphasizing the broader health and environmental implications. METHODS: The largest of the five major chain markets in each district of Istanbul was visited, and adult toothpastes were included in this study. All the constituents that make up the toothpaste were individually recorded in an Excel database. Subsequently, literature regarding the purposes, toxic and potential side effects of each ingredient was gathered using databases such as Google Scholar, PubMed and ScienceDirect. The percentages of these ingredients' occurrence among all the toothpastes were calculated, and the ingredients were categorized into 15 distinct groups based on their usage purposes. RESULTS: There were 160 different varieties of toothpaste belonging to 19 different brands on the market shelves. Although a total of 244 different ingredients were identified, only 78 of them were included in the study. Among the analysed toothpaste types, 105 of them were found to contain 1450 ppm fluoride, whilst 26 toothpaste variants were discovered to have fluoride levels below this value. Among the various ingredients analysed, particular attention was drawn to commonly debated compounds in oral care products. Specifically, titanium dioxide was found in 68% (n = 111) of the varieties, sodium lauryl sulphate in 67% (n = 108) and paraben in 2% (n = 4), respectively. CONCLUSION: Whilst certain ingredients may raise concerns for potential side effects and health considerations within the human body, the toothpaste has long been regarded as an indispensable tool for maintaining optimal oral and dental health. However, gaining a deeper understanding and conducting research on each constituent that comprises the toothpaste, as well as raising awareness in this regard, holds significant importance for human health.