Phase I clinical trial of HC-1119 soft capsule in Chinese healthy adult male subjects: Pharmacokinetics and safety of single-dose proportionality and effects of food.

BACKGROUND: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide. METHODS: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study. RESULTS: In subjects taking HC-1119 soft capsules on fasting, Cmax of HC-1119 prototype increased dose-dependently. Either Cmax and AUC0-∞ of M1 or Cmax of M2 showed statistically significant difference. Dose-proportionality evaluation showed linear pharmacokinetic characteristics in Cmax of HC-1119 prototype, Cmax and AUC0-∞ of M2 in dose range of 40-160 mg. Cmax of HC-1119 was significantly different between the two groups as 160 mg HC-1119 on fasting or after a high-fat diet respectively, while the other parameter were not. HC-1119 and its metabolites M1 and M2 showed a linear dynamic trend. CONCLUSIONS: HC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.

Functional near-infrared spectroscopy during motor imagery and motor execution in healthy adults. / 健康成人运动想象与运动执行期间的近红外脑功能成像.

OBJECTIVES: Studies on the influence of motor imagery (MI) on brain structure and function are limited to traditional imaging techniques and the mechanism for MI therapy is not clear. By observing the brain activation mode during MI and motor execution (ME) in healthy adults, this study aims to use near-infrared brain imaging technology to provide theoretical basis for the treatment of MI. METHODS: A total of 30 healthy adults recruited to the public from June 2021 to August 2021. The MI and ME of the right knee movement served as the task mode. Block design was repeated 5 times alternately in a 20 s task period and a 30 s resting period. The activation patterns of brain regions were compared between the 2 tasks, and the regression coefficient was calculated to reflect the activation intensity of each brain region by Nirspark and SPSS 23.0 softwares. RESULTS: Lane 2, 3, 4, 5, 7, 9, 19, 20, 21, 24, 25, 26, 27, 32, 33, and 34 were significantly activated during the ME task (P<0.05, corrected by FDR) and lane 2, 5, 9, 16, 27, 29, 33, 34, and 35 were significantly activated during the MI task (P<0.05, corrected by FDR). According to the channel brain region registration information, the brain region activation pattern was similar during both MI and ME tasks in healthy adults, including left primary motor cortex (LM1), left primary sensory cortex (LS1), prefrontal pole, Broca area, and right supramarginal gyrus. Both LM1 and left pre-motor cortex (LPMC) were activated during MI in healthy adults, whereas dorsolateral prefrontal cortex (DLPFC) and only LM1 of the motor region were activated during ME. Compared to MI, the activation intensity of left sensory and left motor cortex was significantly enhanced in ME, and that of left and right prefrontal cortex especially left and right pars triangularis Broca's area (P<0.001, corrected by FDR) were significantly enhanced. CONCLUSIONS: The rationality of MI therapy is proved by functional near-infrared spectroscopy. The involvement of DLPFC in motor decision-making may regulate the two-way feedback of premoter cortex-M1 during ME; and Broca area, closely related to the motor program understanding, participates in MI and ME.

The network structure of schema modes.

A fundamental question in psychotherapy is whether interventions should target client problems (i.e., problem-focused approaches) or client strengths (i.e., strength-focused approaches). In this study, we first propose to address this question from a network perspective on schema modes (i.e., healthy or dysfunctional patterns of co-occurring emotions, cognitions, and behaviours). From this perspective, schema modes mutually influence each other (e.g., healthy modes reduce dysfunctional modes). Recent evidence suggests that changes in modes that are strongly associated to other modes (i.e., central modes) could be associated with greater treatment effects. We therefore suggest research should investigate the relative centrality of healthy and dysfunctional modes. To make an exploratory start, we investigated the cross-sectional network structure of schema modes in a clinical (comprising individuals diagnosed with paranoid, narcissistic, histrionic, and Cluster C personality disorders) and non-clinical sample. Results showed that, in both samples, the Healthy Adult was significantly less central than several dysfunctional modes (e.g., Undisciplined Child and Abandoned and Abused Child). Although our study cannot draw causal conclusions, this finding could suggest that weakening dysfunctional modes (compared to strengthening the Healthy Adult) might be more effective in decreasing other dysfunctional modes. Our study further indicates that several schema modes are negatively associated, which could suggest that decreasing one might increase another. Finally, the Healthy Adult was among the modes that most strongly discriminated between clinical and non-clinical individuals. Longitudinal and experimental research into the network structure of schema modes is required to further clarify the relative influence of schema modes.

Prevalence and characteristics of headache attributed to ingestion or inhalation of a cold stimulus (HICS): A cross-sectional study.

BACKGROUND: Headache attributed to ingestion or inhalation of a cold stimulus (HICS), colloquially called ice-cream headache, is a common form of a primary headache in adults and children. However, previous studies on adults are limited due to the small number of patients. Furthermore, most of the subjects in previous studies had a history of other primary headaches. METHODS: Biographic data, clinical criteria of HICS and prevalence of primary headache were collected by a standardized questionnaire. A total of 1213 questionnaires were distributed; the return rate was 51.9% (n = 629); 618 questionnaires could be analyzed. RESULTS: In a cohort of 618 people aged between 17-63 years (females: n = 426, 68.9%), the prevalence of HICS was 51.3% (317 out of 618). There was no difference between men and women (51.3% vs. 51.6%). The duration of HICS was shorter than 30 sec in 92.7%. In the HICS group, localization of the pain was occipital in 17%. Trigemino-autonomic symptoms occurred in 22%, and visual phenomena (e.g. flickering lights, spots or lines) were reported by 18% of the HICS group. The pain intensity, but not the prevalence of HICS, was higher when tension-type headache and migraine or both were present as co-morbid primary headaches (Numeric Rating Scale (NRS) 4.58 and 6.54, p = 0.006). There was no higher risk of participants with migraine getting HICS than for those who did not have migraine (odds ratio = 1.17, 95% confidence interval (CI) 0.75-1.83; p = 0.496). CONCLUSION: The results of this study modified the current criteria for HICS in the ICHD-3 regarding duration and localization. In addition, accompanying symptoms in about one fifth of the participants are not mentioned in the ICHD-3. Neither migraine nor tension-type headache seems to be a risk factor for HICS. However, accompanying symptoms in HICS are more frequent in subjects with another primary headache than in those without such a headache.

Reference Ranges of 8-Isoprostane Concentrations in Exhaled Breath Condensate (EBC): A Systematic Review and Meta-Analysis.

Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress damage. However, no reference range values are available for 8-isoprosante in exhaled breath condensate (EBC) of healthy adults, enabling its meaningful interpretation as a biomarker. We conducted this systematic review and meta-analysis according to the protocol following PROSPERO (CRD42020146623). After searching and analyzing the literature, we included 86 studies. After their qualitative synthesis and risk of bias assessment, 52 studies were included in meta-analysis. The latter focused on studies using immunological analytical methods and investigated how the concentrations of 8-isoprostane differ based on gender. We found that gender had no significant effect in 8-isoprostane concentration. Among other studied factors, such as individual characteristics and factors related to EBC collection, only the device used for EBC collection significantly affected measured 8-isoprostane concentrations. However, adjustment for the factors related to EBC collection, yielded uncertainty whether this effect is due to the device itself or to the other factors. Given this uncertainty, we estimated the reference range values of 8-isoprostane stratified by gender and EBC collection device. A better standardization of EBC collection seems necessary; as well more studies using chemical analytical methods to extend this investigation.

Serologic and viral genome prevalence of HSV, EBV, and HCMV among healthy adults in Wuhan, China.

The worldwide infection rate of herpesvirus is high, but the detailed prevalence in China, especially the central area, remains unclear. In the present study, the prevalence of herpes simplex virus (HSV), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) was investigated in 303 healthy adults in Wuhan, a representative city in Central China. Viral-specific IgG and IgM titers were examined in the serum by chemiluminescent immunoassay, and the existence of viral genomic DNA in blood cells was determined by nested PCR. The overall IgG seroprevalences were 81.5%, 95.4%, and 93.7% for HSV, EBV, and HCMV, while the corresponding IgM seroprevalences were only 6.3%, 2.3%, and 0. The viral genomic DNA of HSV, EBV, and HCMV was identified in the blood samples of 5.9%, 14.2%, and 22.8% of the tested donors, respectively. Significantly, less HSV IgM-positive samples were found in the population over 20 years old than below 20 group; female displayed higher chances for HSV IgG and genome positivity; and occupations such as waiters and medical staffs were shown to be with higher risk for HCMV genome positivity. This study provided useful reference data for the HSV, EBV, and HCMV prevalence in central China, and suggested the potential importance of detecting viral genome to complement serum test data.

Pulmonary Mycobacterium heckeshornense infection in a healthy woman.

Pulmonary infection due to Mycobacterium heckeshornense (M. heckeshornense) in healthy adults without underlying diseases is very rare and optimal treatments have not yet been established. A 39-year-old woman was admitted to our hospital for further examinations following the identification of a pulmonary cavitary nodule. Acid-fast bacilli were cultured from specimens obtained by bronchofiberscopy, and identified with M. heckeshornense using nucleotide sequencing. Antimycobacterial chemotherapy was effective temporarily, while the nodular lesion subsequently worsened. The patient underwent lobectomy and has not relapsed thus far. A lung specimen showed marked granulomatous inflammation with extensive caseous necrosis and the preservation of some parts of alveolar septa within caseous necrosis, indicating an exudative process and resistance to chemotherapy. M. heckeshornense is strongly pathogenic and switching to surgical intervention needs to be considered when chemotherapy is insufficient.

Assessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence.

The objectives of this clinical study were to demonstrate a reduction in exposure to selected harmful and potentially harmful constituents (HPHCs), and to assess product use behavior, in Japanese healthy adult smokers who switched to a novel tobacco vapor product (NTV). 60 smokers were randomly assigned for 5 days to either (a) a group who switched to an NTV (n = 20), (b) a group who continued to smoke their own brand of conventional cigarettes (CC, n = 20) or (c) a smoking abstinence group (SA, n = 20). Fifteen biomarkers of exposure (BoEs) to 14 HPHCs and pyrene were measured at baseline, day 3 and 5. Product use behavior was assessed by measuring product consumption, nicotine uptake and puffing topography. During investigations, increases were observed in product consumption and total puff volume in NTV group subjects as compared to baseline. Additionally, nicotine uptake in the NTV group was approximately half that observed in the CC group. BoE values were significantly reduced in the NTV group as compared to those in the CC group. Significantly, the magnitude of the reduction in exposure to HPHCs observed in the NTV group (49-94%) was close to that observed for the SA group (39-95%).

Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults: A double-blind, randomized, placebo-controlled study.

In a preliminary open-label trial by our group, Bifidobacterium bifidum YIT 10347 (YIT10347) relieved gastric symptoms in patients with functional gastrointestinal disorders. Hence, in this study, we investigated the effects of YIT10347 on gastrointestinal symptoms in healthy adults. In this prospective double-blind, randomized, placebo-controlled trial (UMIN000024654), 100 healthy Japanese adults were randomly assigned to a YIT10347 group or placebo group and consumed 100 mL of YIT10347-fermented milk or placebo fermented milk, respectively, every day for 4 wk. Gastrointestinal symptoms were evaluated by using the modified Frequency Scale for Symptoms of Gastroesophageal Reflux Disease (m-FSSG) and Gastrointestinal Symptom Rating Scale (GSRS) as primary endpoints. Mental symptoms, quality of life, salivary stress markers, and gastric emptying were evaluated as secondary endpoints. Effectiveness and safety were analyzed in a per-protocol set (YIT10347 group, n = 39; placebo group, n = 40) and full analysis set (YIT10347 group, n = 50; placebo group, n = 50), respectively. In the m-FSSG evaluation, the YIT10347 group had a significantly higher relief rate of postprandial discomfort and greater changes in postprandial epigastric pain score from baseline than the placebo group. In the GSRS evaluation, the YIT10347 group had significantly higher relief rates of overall gastrointestinal symptoms, upper gastrointestinal symptoms, flatus, and diarrhea than the placebo group. We detected no significant differences in scores or relief rates of mental symptoms and quality of life, a salivary stress marker, or gastric emptying between the 2 groups. No severe adverse events associated with test beverage consumption were observed in either group. These findings suggest that daily consumption of YIT10347-fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms such as postprandial discomfort and epigastric pain in healthy adults.

The spatial distribution of BUN reference values of Chinese healthy adults: a cross-section study.

The blood urea nitrogen (BUN) is generally regarded as a significant serum marker in estimating renal function. This study aims to explore the geographical distribution of BUN reference values of Chinese healthy adults, and provide a scientific basis for determining BUN reference values of Chinese healthy adults of different regions according to local conditions. A total of 25,568 BUN reference values of healthy adults from 241 Chinese cities were collected in this study, and 17 geographical indices were selected as explanatory variables. The correlation analysis was used to examine the significance between BUN reference value and geographical factors, then five significant indices were extracted to build two predictive models, including principal component analysis (PCA) and support vector regression (SVR) model, then the optimal model was selected by model test to predict BUN reference values of the whole China, finally the distribution map was produced. The results show that BUN reference value of Chinese healthy adult was characteristically associated with latitude, altitude, annual mean temperature, annual mean relative humidity, and annual precipitation. The model test shows, compared with SVR model, the PCA model possesses superior simulative and predictive ability. The distribution map shows that the BUN reference values of Chinese healthy adult are lower in the east and higher in the west. These results indicate that the BUN reference value is significantly affected by geographical environment, and the BUN reference values of different regions could be seen clearly on distribution map.

Pharmacokinetics of nicotine following the controlled use of a prototype novel tobacco vapor product.

The objective of this clinical study was to investigate the pharmacokinetics of nicotine following the use of a prototype novel tobacco vapor (PNTV) product in comparison to a conventional cigarette (CC1). The study was conducted in Japanese healthy adult male smokers, using an open-label, randomized, two-period crossover design, to assess the pharmacokinetics of nicotine after controlled use of a PNTV product or CC1. During the study period, blood samples were drawn from subjects for the measurement of plasma nicotine concentrations and nicotine intake was estimated from the mouth level exposure (MLE). The Cmax and AUClast following the use of PNTV product were 45.7% and 68.3%, respectively, of those obtained with CC1 and there were no significant differences in the tmax and t1/2 between PNTV product and CC1. The estimated MLE following the use of PNTV product was approximately two-thirds of that obtained following the smoking of CC1, but the relative bioavailability of PNTV product to CC1 was approximately 104%. The differences in Cmax and AUClast between PNTV product and CC1 therefore are explained by differences in nicotine intake. These results suggest that the PNTV product shows a similar pharmacokinetic profile to CC1, while delivering less nicotine following controlled use.

Characterization of left ventricle energy loss in healthy adults using vector flow mapping: Preliminary results.

BACKGROUND: Energy loss (EL) is a new quantitative hemodynamic index based on vector flow mapping (VFM). This study aimed to characterize EL of the left ventricle (LV) in healthy adults. METHODS: Fifty-one healthy adults were enrolled in this study. EL of LV was analyzed frame by frame using color Doppler images of a standard apical three-chamber dynamic view on an offline VFM workstation. The average EL of systole and diastole was calculated, and the results were averaged over three cardiac cycles. RESULTS: The average EL for systole and diastole was 11.07±5.82J/m/s and 11.58±5.54 J/m/s, respectively. Multivariate regression analysis showed that the aortic velocity time integral (AOVTI), A-wave peak velocity, and isovolumetric contraction time (IVCT) were independently associated with the average systolic EL. E-wave peak velocity, height, and IVCT were independently associated with the average diastolic EL. For females, the average systolic and diastolic EL was 12.66±7.06J/m/s and 13.90±5.37J/m/s, respectively. For males, the systolic and diastolic EL was 9.29±3.33J/m/s and 8.97±4.55J/m/s, respectively. CONCLUSIONS: Energy loss in LV changes regularly during the cardiac cycle. The average systolic EL has a high positive correlation with AOVTI, whereas the average diastolic EL has with E-wave peak velocity. Women have higher average EL than men in both systole and diastole. By recognizing the EL characterization of healthy adults, the variation in EL may reflect cardiac dysfunction. These were preliminary results, and thus, the clinical implications of EL warrant further investigation.

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

BACKGROUND: Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. METHODS: In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. RESULTS: The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). CONCLUSION: The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform ( KCT0000258 ).

The effect of oral synbiotics on the gut microbiota and inflammatory biomarkers in healthy adults: a systematic review and meta-analysis.

CONTEXT: Prior research has explored the effect of synbiotics, the combination of probiotics and prebiotics, on the gut microbiota in clinical populations. However, evidence related to the effect of synbiotics on the gut microbiota in healthy adults has not been reviewed to date. OBJECTIVE: A systematic review and meta-analysis was conducted to comprehensively investigate the effect of synbiotics on the gut microbiota and inflammatory markers in populations of healthy adults. DATA SOURCES: Scopus, PubMed, Web of Science, ScienceDirect, MEDLINE, CINAHL, and The Cochrane Library were systematically searched to retrieve randomized controlled trials examining the primary outcome of gut microbiota or intestinal permeability changes after synbiotic consumption in healthy adults. Secondary outcomes of interest were short-chain fatty acids, inflammatory biomarkers, and gut microbiota diversity. DATA EXTRACTION: Weighted (WMD) or standardized mean difference (SMD) outcome data were pooled in restricted maximum likelihood models using random effects. Twenty-seven articles reporting on 26 studies met the eligibility criteria (n = 1319). DATA ANALYSIS: Meta-analyses of 16 studies showed synbiotics resulted in a significant increase in Lactobacillus cell count (SMD, 0.74; 95% confidence interval [CI], 0.15, 1.33; P = 0.01) and propionate concentration (SMD, 0.22; 95% CI, 0.02, 0.43; P = 0.03) compared with controls. A trend for an increase in Bifidobacterium relative abundance (WMD, 0.97; 95% CI, 0.42, 2.52; P = 0.10) and cell count (SMD, 0.82; 95% CI, 0.13, 1.88; P = 0.06) was seen. No significant differences in α-diversity, acetate, butyrate, zonulin, IL-6, CRP, or endotoxins were observed. CONCLUSION: This review demonstrates that synbiotics modulate the gut microbiota by increasing Lactobacillus and propionate across various healthy adult populations, and may result in increased Bifidobacterium. Significant variations in synbiotic type, dose, and duration should be considered as limitations when applying findings to clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42021284033.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Effects of low-load blood flow restriction training in healthy adult tendons: A systematic review and meta-analysis.

OBJECTIVE: To systematically review the effects of low-load blood flow restriction training (LL-BFR) on healthy adult tendons. DESIGN: A systematic review with meta-analysis. LITERATURE SEARCH: Six electronic databases were searched by two researchers. STUDY SELECTION CRITERIA: Clinical trials comparing the effects of LL-BFR to high-load resistance training (HL-RT) or low-load resistance training (LL-RT) in healthy adult tendons. DATA SYNTHESIS: Two reviewers selected the eligible clinical trials, and one reviewer exported the data. Two reviewers evaluated the study quality and risk of bias using the PEDro scale and the ROB2 scale. We performed meta-analysis where appropriate using a random-effects model. We rated the quality of evidence using GRADE. RESULTS: Six studies were eligible. We analyzed tendon cross-sectional area (CSA) and tendon stiffness as the outcomes. Across all comparisons, there was low-to moderate-quality evidence of a difference between LL-BFR and LL-RT immediately after exercise. There was high-quality evidence of no difference between LL-BFR and HL-RT in the long term. CONCLUSION: The effects of LL-BFR on the tendons depends on the time and dose of the intervention. LL-BFR could be useful to increase the CSA of the tendons in a similar or superior way to HL-RT after 8 weeks of intervention.

The Effect of Thickened Water on Ciprofloxacin Pharmacokinetics: A Comparative Study in Adult Males.

Background/Objectives: The use of food thickeners with ciprofloxacin tablets may result in a gelatinous appearance and experience delayed dissolution, which presents a challenge for the drug's efficacy, creating a healthcare economic issue. However, the pharmacokinetic impact of this compound in humans remains uncertain. Therefore, a comparative pharmacokinetic study of ciprofloxacin was conducted on healthy adult Japanese males. Methods: We compared the effects of administering tablets with water or thickened water and crushed tablets mixed with thickened water. The maximum blood concentration (Cmax) of ciprofloxacin determines the drug's efficacy. Results: There were variations in drug absorption across different administration methods. The group who took the tablets immersed in thickened water exhibited different results in the area under the blood drug concentration-time curve (AUC) and Cmax compared to the group who took the tablets in regular water. Notably, the group that consumed the crushed tablets mixed with thickened water demonstrated equivalent results for both AUC and Cmax. Conclusions: Administering crushed tablets in thickened water may yield pharmacokinetics comparable to those of tablets taken with water. However, the process of crushing tablets may result in the loss of active ingredients and compromise the formulation, necessitating a comprehensive assessment before administration.

The normative values of pain thresholds in healthy Taiwanese.

OBJECTIVE: Quantitative sensory testing is widely used in clinical and research settings to assess the sensory functions of healthy subjects and patients. It is of importance to establish normative values in a healthy population to provide reference for studies involving patients. Given the absence of normative values for pain thresholds in Taiwan, the aim of this study was to report the normative values for future reference in the Taiwanese population and compare the differences between male and female participants. METHODS: Healthy adults without any chronic or acute pain condition were recruited. The pain thresholds were assessed over the cephalic (supraorbital area and masseter muscle) and extracephalic (medio-volar forearm and thenar eminence) areas. The heat, cold, mechanical punctate, and pressure pain thresholds were measured with a standardized protocol. Comparisons between male and female participants were performed. RESULTS: One hundred and thirty healthy participants (55 males: 30.4 ± 7.4 years; 75 females: 30.5 ± 8.1 years) finished the assessments. Male participants were less sensitive to mechanical stimuli, including pressure over masseter muscle (male vs. female: 178.5 ± 56.7 vs. 156.6 ± 58.4 kPa, p = .034) and punctate over medio-volar forearm (male vs. female: 116.4 ± 45.2 vs. 98.7 ± 65.4 g, p = .011), compared to female participants. However, female participants were less sensitive to cold stimuli, indicated by lower cold pain thresholds over the supraorbital area (male vs. female: 18.6 ± 8.4 vs. 13.6 ± 9.3°C, p = .004), compared to male participants. No significant differences were found between sexes in other pain threshold parameters. CONCLUSIONS: We provided the normative values of healthy male and female adults in Taiwan. This information is crucial for comparison in future pain-related studies to identify potential hypoalgesia or hyperalgesia of tested subjects.

Effects of Lactoferrin on Oral and Throat Conditions under Low Humidity Environments: A Randomized, Double-Blind, and Placebo-Controlled Crossover Trial.

To evaluate the effects of a single ingestion of bovine lactoferrin (bLF) on oral and throat conditions under a low-humidity environment. A randomized, double-blind, 2-sequence, 2-treatment, and 2-period placebo-controlled crossover trial was conducted. Healthy adult subjects orally ingested bLF dissolved in water, or placebo water, followed by exposure to low humidity (20 °C, 20% relative humidity (RH)) for 2 h. The primary endpoint was subjective oral and throat discomfort assessed by a visual analog scale (VAS), which positively correlated with the discomfort. Secondary endpoints were unstimulated whole salivary flow rate (UWSFR) and salivary immunoglobulin A (IgA) secretion rate. Overall, 40 subjects were randomly assigned to two sequences (20 each) and 34 were analyzed. The VAS values for oral and throat discomfort in the bLF treatment were significantly lower than in the placebo treatment, whereas UWSFR and IgA secretion rates were comparable between the two treatments. Adverse drug reactions were not observed. Subjective oral and throat discomfort associated with low humidity is suppressed by a single ingestion of bLF. Our findings demonstrate the novel use of bLF in a clinical situation that leverages its unique characteristics.

Sternoclavicular septic arthritis in a healthy adult: A case report and a review of the literature.

Sternoclavicular joint septic arthritis is rare and commonly associated with specific risk factors. We report the case of a 58-year-old female with no previous medical or surgical history who presented complaining of a warm, indurated mass overlying the right sternoclavicular joint. Computed tomography of the chest showed erosion of the sternal end of the clavicle and the manubrium sternum associated with thickening of the synovium and a sternoclavicular joint space narrowing, suggestive of an infective process. Intraoperative finds a purulent collection extending both over the clavicle and the sternum. Limited destruction of small parts of the sternoclavicular joint was noted. The abscess was drained. Simple debridement and limited curettage were preferred to en bloc resection given the limited size of necrotic tissues. Sternoclavicular joint septic arthritis is a condition with significant morbidity and potential mortality. All medical practitioners must maintain a high degree of suspicion, even in healthy patients, as it can lead to serious complications.