Clinical research advances of CFHR5 nephropathy: a recent review.

CFHR5 nephropathy is a type of clinical C3 glomerulopathy, which is a monogenic genetic disease caused by the internal replication of CFHR5 gene, a protein related to the complement regulatory factor H family. The disease seems to be prevalent only in people of Greek Cypriot descent. Because of the special variation of the internal replication of exon 2 and exon 3 of CFHR5 protein in the occurrence of disease, it has had a serious impact on local residents. At present, the mechanism of glomerular damage caused by CFHR5 protein mutations is still unclear. The purpose of this article is to review the clinical research advances of this disease in the past 10 years, including the study of mutant genes, the analysis of mutant proteins and the role of alternative pathways in glomerular injury. It covers the progress in diagnosis and clinical treatment of the disease and looks forward to the future development prospects of its treatment. It is hoped that the recent results will be summarized for the follow-up in-depth study of CFHR5 nephropathy.

Concurrent Chemotherapy and Pelvic Radiation Therapy Compared With Pelvic Radiation Therapy Alone as Adjuvant Therapy After Radical Surgery in High-Risk Early-Stage Cancer of the Cervix.

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA2, IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m2 and a 96-hour infusion of fluorouracil 1,000 mg/m2/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P = .003) and 1.96 (P = .007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Immune-mediated hematological disease in dogs is associated with alterations of the fecal microbiota: a pilot study.

BACKGROUND: The dog is the most popular companion animal and is a valuable large animal model for several human diseases. Canine immune-mediated hematological diseases, including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP), share many features in common with autoimmune hematological diseases of humans. The gut microbiome has been linked to systemic illness, but few studies have evaluated its association with immune-mediated hematological disease. To address this knowledge gap, 16S rRNA gene sequencing was used to profile the fecal microbiota of dogs with spontaneous IMHA and ITP at presentation and following successful treatment. In total, 21 affected and 13 healthy control dogs were included in the study. RESULTS: IMHA/ITP is associated with remodeling of fecal microbiota, marked by decreased relative abundance of the spirochete Treponema spp., increased relative abundance of the pathobionts Clostridium septicum and Escherichia coli, and increased overall microbial diversity. Logistic regression analysis demonstrated that Treponema spp. were associated with decreased risk of IMHA/ITP (odds ratio [OR] 0.24-0.34), while Ruminococcaceae UCG-009 and Christensenellaceae R-7 group were associated with increased risk of disease (OR = 6.84 [95% CI 2-32.74] and 8.36 [95% CI 1.85-71.88] respectively). CONCLUSIONS: This study demonstrates an association of immune-mediated hematological diseases in dogs with fecal dysbiosis, and points to specific bacterial genera as biomarkers of disease. Microbes identified as positive or negative risk factors for IMHA/ITP represent an area for future research as potential targets for new diagnostic assays and/or therapeutic applications.

[Application status of CFD technology in occupational hazard control].

In the process of occupational hazard management, computational fluid dynamics technology can be used to reflect the distribution pattern of occupational hazards in the production process, so as to quickly and accurately guide the formulation of occupational disease prevention and control programs. This paper summarizes and analyzes the current research results on the prevention and control of occupational hazards in workplaces through computational fluid dynamics technology, and describes the application of these research results in the process of occupational disease prevention and control. On this basis, this paper presents the problems and application limitations of existing research and points out the future key research directions, which are of great reference value for guiding further systematic and in-depth research on simulation, experimentation and management of occupational hazards that can cause occupational diseases.

[Study on the diffusion of hydrogen fluoride in an electrolytic fluoride plant based on CFD numerical simulation method].

Objective: Using CFD technology to grasp the distribution and diffusion of hydrogen fluoride in an electrolytic fluorine plant, provide guidance and scientific basis for enterprises to carry out occupational health management in enterprises, install hazardous substance alarm devices, and protect workers' occupational health. Methods: In July 2019, the diffusion law of hydrogen fluoride gas produced in an electrolytic fluorine plant is selected as the research object. Through the establishment of models and grids, the Fluent numerical simulation method is finally used to simulate the diffusion and distribution of hydrogen fluoride gas under ventilation conditions. Results: The results showed that the average concentration of hydrogen fluoride was 0.045 mg/m(3) in the workplace, and the absorbed zone height (1.5 m) was 0.02 mg/m(3) in the inspection channel, which was in accordance with the national standard. However, there is eddy current above the electrolyzer near the inlet, may lead to the accumulation of hydrogen fluoride gas. Conclusion: The research of CFD numerical simulation method on the distribution and diffusion of hydrogen fluoride concentration in electrolytic fluorine plant can be applied to the prevention, control and management of occupational hazards in electrolytic fluorine plant.

Orbital stability analysis and photometric characterization of the second Earth Trojan asteroid 2020 XL5.

Trojan asteroids are small bodies orbiting around the L4 or L5 Lagrangian points of a Sun-planet system. Due to their peculiar orbits, they provide key constraints to the Solar System evolution models. Despite numerous dedicated observational efforts in the last decade, asteroid 2010 TK7 has been the only known Earth Trojan thus far. Here we confirm that the recently discovered 2020 XL5 is the second transient Earth Trojan known. To study its orbit, we used archival data from 2012 to 2019 and observed the object in 2021 from three ground-based observatories. Our study of its orbital stability shows that 2020 XL5 will remain in L4 for at least 4 000 years. With a photometric analysis we estimate its absolute magnitude to be [Formula: see text], and color indices suggestive of a C-complex taxonomy. Assuming an albedo of 0.06 ± 0.03, we obtain a diameter of 1.18 ± 0.08 km, larger than the first known Earth Trojan asteroid.

[Analysis of prescription and rationality of anti-hypertensive medication among community health centers in Beijing].

Objective: Explore the usage of anti-hypertension drugs and the rationality of hypertension prescription among the primary health centers in Dongcheng District, Beijing. Method: This cross-sectional and retrospective study was applied to analyze the hypertension prescriptions from the 8 community health centers in Dongcheng District. The anatomical, therapeutic and chemical classification (ATC) codes were used to determine the drug category. ATC information was used to filter data containing antihypertensive drugs, and group the number and proportion of ATC categories. The type of drug was judged by its generic name. According to the diagnosis information in the prescription, the prescription containing the Western medicine diagnosis of hypertension was screened out. The comorbidities of hypertension in the study included 7 types of diseases including diabetes, chronic kidney disease, coronary heart disease, heart failure, atrial fibrillation, stroke, and dyslipidemia. The analysis of prescription rationality included rationality of combination medication, rationality of drug dosage and rationality of drug price. The agreed daily dose (DDD) method was used to analyze the rationality of drug dosage. The drug utilization index (DUI) was used as a quantitative indicator to estimate the rationality of medication, and overdose was expressed by DUI>1. The reasonableness of the drug price was judged based on the price of the drug and whether it was a drug in the "4+7" plan. Results: A total of 658 140 prescriptions were extracted as the final data set, involving 7 categories and 60 commonly used anti-hypertensive drugs, and the corresponding cost of medication was ï¿¥96.58 million. Drugs were prescribed according to comorbidities, and the choice followed the international guidelines. Calcium channel blockers (CCB) were the most prescribed drugs in the prescriptions of patients with comorbidities, and α-adrenergic receptor antagonists were the least prescribed drugs. The proportion of diuretics prescribed in hypertensive patients complicating with heart failure was 21.17% (505/2 385), which was much higher than that of patients complicating with other comorbidities (P<0.05). The proportion of diuretics prescribed in hypertension patients complicating with dyslipidemia was lower than that of patients with other comorbidities (2 639 (0.94%), P<0.05), and ß-blockers (BB) or angiotensin Ⅱreceptor blockers (ARB) were more likely to be selected (BB: 59 348 (21.08%), ARB: 51 356 (18.24%))in these patients. The proportion of BB in prescriptions for hypertension patients with chronic kidney disease was lower than that of patients with other comorbidities (P<0.05). The proportion of BB in prescriptions for hypertension patients with coronary heart disease was higher than that of other comorbidities (P<0.05). Hypertension patients with atrial fibrillation or stroke accounted for a higher proportion of CCB prescriptions (P<0.05). Single antihypertensive drug prescriptions accounted for the highest proportion, 61.19% (402 745/658 140). Two-combination prescriptions accounted for the highest proportion of combination prescriptions, 72.19% (184 392/255 395). CCB based two-combination prescriptions accounted for the highest proportion, 122 350(66.36%). ARB-based tri-combination prescriptions accounted for the highest proportion, 48 915(89.50%),followed by CCB based tri-combination prescriptions (44 732(81.85%)).There were 2 174 (0.33%) prescriptions with unreasonable combination therapies and DUI>1 were found in 48 out of 60 commonly used drugs. In all possible antihypertensive drugs, only 40.92% (109 227/266 993)followed the "4+7" plan. Conclusions: The anti-hypertensive agents from these prescriptions in the primary health centers are diverse, and the choice is generally complied with the guidelines, but some unreasonable situations existed, especially on the combined anti-hypertensive medication, overdose, and"4+7"plan is not followed completely.

[Investigation on two family clusters of COVID-19 in a county of Baotou city in Inner Mongolia Autonomous Region].

Objective: To investigate the epidemiological characteristics and transmission chain of COVID-19 in two families, and to provide scientific evidence for effective prevention and control measures. Methods: Field epidemiological investigation was conducted for the COVID-19 cases occurred in two families and the close contacts in a county of Baotou city in Inner Mongolia Autonomous Region. Descriptive statistical analysis on epidemiological data was conducted. Results: The infection source of the COVID-19 cases in the two families was a man who had living history in Wuhan. After his return, his parents were infected by him. A few days later, the members of a neighbor family were found to be infected, and relatives of this family were also infected after dining together repeatedly. Finally, ten confirmed cases and three suspected cases of COVID-19 were detected in the two families. Conclusions: Human-to-human transmission of COVID-19 can occur not only in a family but also in neighborhoods. The cases in two families had close relationship, indicating the necessity to strengthen the health education about COVID-19 prevention and control and the management of groups at high risk to reduce the incidence of COVID-19 in families and neighborhoods.

[Evaluation of the emergency response strategies and measures on the epidemic of COVID-19 in Shenzhen, China].

Objectives: This study aimed to evaluate the effect of the strategies on COVID-19 outbreak control in Shenzhen, and to clarify the feasibility of these strategies in metropolitans that have high population density and strong mobility. Methods: The epidemic feature of COVID-19 was described by different phases and was used to observe the effectiveness of intervention. Hierarchical spot map was drawn to clarify the distribution and transmission risk of infection sources at different time points. The Susceptible-Exposed-Infectious-Asymptomatic-Recovered model was established to estimate case numbers without intervention and compare with the actual number of cases to determine the effect of intervention. The positive rate of the nucleic acid test was used to reflect the risk of human exposure. A survey on COVID-19 related knowledge, attitude and behaviors were used to estimate the abilities of personal protection and emergency response. Results: The epidemic of COVID-19 in Shenzhen experienced the rising, plateau and decline stage. The case number increased rapidly at the beginning, with short duration of peak period. Although the epidemic curve showed human-to-human transmission, the "trailing" was not obvious. From the spot map, during the intervention period, the source of infection was widely distributed. More cases and higher transmission risk were observed in areas with higher population density. After the effective intervention measures, both infection sources and the risk of transmission decreased. After compared with the estimated case numbers without intervention, actual number proved the COVID-19 control strategies were effective. The positive rate of nucleic acid test for high risk populations decreased and no new cases reported since February 16. Shenzhen citizens had high knowledge, attitude and behavior level, and high protection ability and emergency response. Conclusions: Although the response initiated by the health administration department played a key role at the early stage of the epidemic, it was not enough to contain the outbreak of COVID-19. The first-level emergency response initiated by provincial and municipal government was effective and ensured the start of work resumption after the Spring Festival. Metropolitans like Shenzhen can also achieve the goals of strategies and measures for containment and mitigation of COVID-19.

Venous Vascular Closure System Versus Manual Compression Following Multiple Access Electrophysiology Procedures: The AMBULATE Trial.

OBJECTIVES: This study compared the efficacy and safety of the VASCADE MVP Venous Vascular Closure System (VVCS) device (Cardiva Medical, Santa Clara, California) to manual compression (MC) for closing multiple access sites after catheter-based electrophysiology procedures. BACKGROUND: The VASCADE MVP VVCS is designed to provide earlier ambulatory hemostasis than MC after catheter-based procedures. METHODS: The AMBULATE (A Randomized, Multi-center Trial to Compare Cardiva Mid-Bore [VASCADE MVP] VVCS to Manual Compression in Closure of Multiple Femoral Venous Access Sites in 6 - 12 Fr Sheath Sizes) trial was a multicenter, randomized trial of device closure versus MC in patients who underwent ablation. Outcomes included time to ambulation (TTA), total post-procedure time (TPPT), time to discharge eligibility (TTDe), time to hemostasis (TTH), 30-day major and minor complications, pain medication usage, and patient-reported outcomes. RESULTS: A total of 204 patients at 13 sites were randomized to the device arm (n = 100; 369 access sites) or the MC arm (n = 104; 382 access sites). Baseline characteristics were similar between groups. Mean TTA, TPPT, TTDe, and TTH were substantially lower in the device arm (respective decreases of 54%, 54%, 52%, and 55%; all p < 0.0001). Opioid use was reduced by 58% (p = 0.001). There were no major access site complications. Incidence of minor complications was 1.0% for the device arm and 2.4% for the MC arm (p = 0.45). Patient satisfaction scores with duration of and comfort during bedrest were 63% and 36% higher in device group (both p < 0.0001). Satisfaction with bedrest pain was 25% higher (p = 0.001) for the device overall, and 40% higher (p = 0.002) for patients with a previous ablation. CONCLUSIONS: Use of the closure device for multiple access ablation procedures resulted in significant reductions in TTA, TPPT, TTH, TTDe, and opioid use, with increased patient satisfaction and no increase in complications. (A Randomized, Multi-center Trial to Compare Cardiva Mid-Bore VVCS to Manual Compression in Closure of Multiple Femoral Venous Access Sites in 6 - 12 Fr Sheath Sizes [AMBULATE]; NCT03193021).

Microring resonator-assisted Fourier transform spectrometer with enhanced resolution and large bandwidth in single chip solution.

Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.

Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men.

BACKGROUND: Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone® (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical. OBJECTIVE: Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups. DESIGN: We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment. RESULTS: Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels. CONCLUSION: Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.

Preventing secondary exposure to women from men applying a novel nestorone/testosterone contraceptive gel.

BACKGROUND: Testosterone (T)/Nestorone (NES) combination gel is a potential transdermal male contraceptive that suppresses gonadotropins and spermatogenesis. Transfer of transdermal T from men to women can be prevented by washing or covering application sites with clothing. OBJECTIVES: We hypothesized that showering or wearing a shirt over gel application sites would prevent secondary exposure of T and NES to a woman after close skin contact. MATERIALS AND METHODS: Twelve healthy male and 12 healthy female participants were recruited. Men applied T/NES 62 mg/8 mg gel to their shoulders and upper arms. Two hours after application, female partners rubbed the application site for 15 min. Exposure in the female partner was assessed under three conditions: a shirt covered the application site; the man showered prior to skin contact; or without intervention to reduce transfer. Serum T and NES concentrations were measured by LC-MS/MS in serial blood samples for 24 h after gel exposure. MAIN OUTCOMES: Change in female serum T and NES levels as measured by average concentration over 24 h (Cavg ). RESULTS: Median female serum T Cavg was 23.9 ng/dL (interquartile range, 19.3, 33.9) with the shirt barrier and 26.7 ng/dL (20.7, 33.9) after showering, which was higher than baseline 20.9 ng/dL (16.7, 25.0), both p < 0.03) but lower than without intervention (58.2 ng/dL [30.9, 89.1], both p < 0.01). Female serum NES Cavg and maximum concentration were below the lower limit of quantification with the shirt barrier and after showering, but increased without intervention in six of 12 women (maximum concentration <60 pg/mL). Men had lower average serum NES levels after showering (47 pg/ml [20, 94] compared to no intervention (153.3 pg/mL [51, 241], p < 0.02). CONCLUSION: Secondary transfer of T and NES occurs after intensive skin contact with the gel application site. Secondary transfer is decreased by a shirt barrier or showering before contact.

[Glucocorticoids and liver diseases].

Glucocorticoids is a type of steroid hormone secreted from zona fasciculata of adrenal cortex.As an immune and inflammatory inhibitor, glucocorticoids has been used to treat many kinds of diseases.T cell response plays a crucial role in the pathogenesis of liver diseases. However, the role of glucocorticoids in the mechanism and treatment of liver disease in current clinical practice is controversial. This paper summarizes the progress of glucocorticoid use for the treatment of liver diseases in recent years. References will be provided for how to grasp the indications,application timing and proper dosage of glucocorticoids in liver diseases.

Are older drivers' driving patterns during an on-road driving task representative of their real-world driving patterns?

OBJECTIVE: The current study investigated whether older drivers' driving patterns during a customized on-road driving task were representative of their real-world driving patterns. METHODS: Two hundred and eight participants (male: 68.80%; mean age = 81.52 years, SD = 3.37 years, range = 76.00-96.00 years) completed a customized on-road driving task that commenced from their home and was conducted in their own vehicle. Participants' real-world driving patterns for the preceding 4-month period were also collected via an in-car recording device (ICRD) that was installed in each participant's vehicle. RESULTS: During the 4-month period prior to completing the on-road driving task, participants' median real-world driving trip distance was 2.66 km (interquartile range [IQR] = 1.14-5.79 km) and their median on-road driving task trip distance was 4.41 km (IQR = 2.83-6.35 km). Most participants' on-road driving task trip distances were classified as representative of their real-world driving trip distances (95.2%, n = 198). CONCLUSIONS: These findings suggest that most older drivers were able to devise a driving route that was representative of their real-world driving trip distance. Future research will examine whether additional aspects of the on-road driving task (e.g., average speed, proportion of trips in different speed zones) are representative of participants' real-world driving patterns.

Modulation of digital flexor tendon healing by vascular endothelial growth factor gene transfection in a chicken model.

A major challenge in tendon injury is the weak intrinsic healing capacity of tendon that may cause rupture of the repair after surgery. Growth factors are believed to be critical during tendon healing. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. A total of 128 deep flexor tendons in the long toes of chickens were completely transected and injected with 2 × 109 particles of AAV2-VEGF or saline before surgically repaired. At postoperative 4, 6 and 8 weeks, the gliding excursions of tendon were recorded and adhesions around the repair site scored. At 2, 4, 6 and 8 weeks, the ultimate strengths of the healing tendons were tested. Terminal deoxynucleotide transferase dUTP nick end labeling assay were performed to detect cellular apoptosis and immunofluorescence staining to detect type III collagen and matrix metalloprotease-2 (MMP2) expression in tendon tissues. The gliding excursion and adhesion score were similar between AAV2-VEGF-treated tendons and the control tendons. Delivery of AAV2-VEGF significantly increased ultimate strength of the healing tendons at postoperative 4, 6 and 8 weeks (P<0.05). Apoptotic reaction was inhibited from postoperative 2 to 8 weeks in tendon core area or surface area. Type III collagen expression was enhanced at 2, 4, 6 and 8 weeks and MMP2 expression enhanced at 2 and 4 weeks after AAV2-VEGF transfection. The current study confirms the therapeutic efficacy of AAV2-VEGF in improving healing strength of tendon without aggravating adhesion formation after tendon injury, shedding light on the application of molecular therapy in modulating tendon healing.

Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

Dimethandrolone (DMA, 7α,11ß-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be advantageous for the application of DMAU as a male contraceptive.

Predicting the aquatic toxicity mode of action using logistic regression and linear discriminant analysis.

The paper highlights the use of the logistic regression (LR) method in the construction of acceptable statistically significant, robust and predictive models for the classification of chemicals according to their aquatic toxic modes of action. Essentials accounting for a reliable model were all considered carefully. The model predictors were selected by stepwise forward discriminant analysis (LDA) from a combined pool of experimental data and chemical structure-based descriptors calculated by the CODESSA and DRAGON software packages. Model predictive ability was validated both internally and externally. The applicability domain was checked by the leverage approach to verify prediction reliability. The obtained models are simple and easy to interpret. In general, LR performs much better than LDA and seems to be more attractive for the prediction of the more toxic compounds, i.e. compounds that exhibit excess toxicity versus non-polar narcotic compounds and more reactive compounds versus less reactive compounds. In addition, model fit and regression diagnostics was done through the influence plot which reflects the hat-values, studentized residuals, and Cook's distance statistics of each sample. Overdispersion was also checked for the LR model. The relationships between the descriptors and the aquatic toxic behaviour of compounds are also discussed.