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Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. Being the largest possible meta-analysis at this time, it encompasses all known records of animal lethality studies over the past 100 years. These results were not artifacts of resistant test-animal species and showed orders of magnitude beyond the 1.6 logs (40-fold change) range of lethal dose documented in the literature between amphibians, lizards, and mice., Methods: A total of 1003 lethal dose study results for 160 of the most lethal venomous ophidian species in the world were analyzed., Results: LDLo was not different from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that, for the route of inoculation, IC < IV < IP < IM < SC was well supported (R 2 = 0.90). However, 5% of ICs were the highest dose, and 7% of SC inoculations were the lowest dose. Within the mouse test species, for one route of inoculation, the widest LD range was 2.96 logs (917-fold change, N = 20). Within mouse species, for multiple routes of inoculation, the widest LD range was 3.6 logs (4,150-fold change, N = 20). The strongest correlation for the range of lethal dose results was the number of studies (R 2 = 0.56), followed by the number of test-animal species (R 2 = 0.55) and then the number of routes of inoculation (R 2 = 0.43)., Conclusion: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate mean, median, minimum, range, and standard deviation as shown in the supplement spreadsheet, and the equations we provide. Standard deviation multiples may provide the desired safety for experimenters. For estimating the LD50 range and minimum lethal dose for species with little data, we recommend curating a meta-dataset of related snakes, and computational research to strengthen this estimation., Competing Interests: The authors declare no competing interests., (© 2024 The Journal of Biological Methods, All rights reserved.)

Here presented for the first time are results showing persistence over a 5+ year period in a human who had a hormone gene therapy administered to muscle. This growth hormone releasing hormone (GHRH) therapy was administered in two doses, a year apart, with a mean after the second dose of 195 ng/mL (13 × normal, σ = 143, σ M  = 34, max = 495, min = 53). This level of GHRH therapy appears to be safe for the subject, although there were some adverse events. Insulin-like growth factor 1 levels were little affected, nor were the growth hormone test results, showing no indications of acromegaly for the hormone homologue used. Heart rate declined 8 to 13 bpm, persistent over 5 years. Testosterone rose by 52% (σ = 22%, σ M  = 6%). The high-density lipoprotein/low-density lipoprotein ratio dropped from 3.61 to mean 2.81 (σ = 0.26, σ M  = 0.057, max = 3.3, min = 2.5), and triglycerides declined from 196 mg/dL to mean 94.4 mg/dL (σ = 21.9, σ M  = 5.0, min = 59, max = 133, min = 59). White blood cell counts increased, however, the baseline was not strong. CD4 and CD8 mean increased by11.7% (σ = 11.6%, σ M  = 3.3%, max = 30.7%, min = -9.6%) and 12.0% (σ = 10.5%, σ M  = 3.0%, max = 29.1%, min = -6.7%), respectively. Ancillary observations comprise an early period of euphoria, and a dramatic improvement in visual correction after the first dose, spherical correction from baseline (L/R) -2.25/-2.75 to -0.25/-0.5. Over the next 5 years, correction drifted back to -1.25/-1.75. Horvath PhenoAge was cut 44.1% post-treatment. At completion, epigenetic age was -6 years (-9.3%), and telomere age was +7 months (+0.9%).

We examine self-experimentation ethics history and practice, related law, use scenarios in universities and industry, and attitudes. We show through analysis of the historical development of medical ethics and regulation, from Hippocrates through Good Clinical Practice that there are no ethical barriers to self-experimentation. When the self-experimenter is a true investigator, there is no other party to be protected from unethical behavior. We discuss the n-of-1 issue in self-experiments, and make suggestions for improving experiment design. We discuss real-world scenarios of self-experimentation: at universities, for independent single-subject investigators, investigator/employees at pharmaceutical firms, and nonscientist self-experimenters. Our survey of ethics committees regarding policy and review for self-experimenting investigators show that approximately one-third of ethics committee respondents had a policy regarding self-experimentation, and one-third did not require ethical committee review of proposed experiments. There was no relationship between having a policy and asking for review. We also surveyed member attitudes to, and experiences of, self-experimentation among members of the National Academy of Sciences, Royal Society, and European Academy of Sciences. To our knowledge, this survey is the first breakdown of self-experiments into impact-relevant type classifications, and represents an advance in the field. Half of our scientist respondents performed self-experiments, and roughly one-fifth had conducted serious self-experiments. Most responders thought self-experiments were valuable, however, biologics injections, radiation exposure, and surgical implants had negative ratings greater than positive. We conclude that self-experimenters should not have attempts made to terminate them, bar them from use of facilities, nor be barred from using themselves or their tissues except in exceptional circumstances. Organizational uncertainty over the ethical and regulatory status of self-experimentation, and resulting fear of consequences is unjustified and may be blocking a route to human experiments that practicing scientists widely consider appropriate, and which historical precedent has shown is valuable.

Obesity is the major risk factor for early puberty, but emerging evidence indicates other factors including psychosocial stress. One key brain region notable for its role in controlling calorie intake, stress, and behavior is the amygdala. Early studies involving amygdala lesions that included the medial nucleus advanced puberty in rats. More recently it was shown that a critical site for lesion-induced hyperphagia and obesity is the posterodorsal subnucleus of the medial amygdala (MePD), which may explain the advancement of puberty. Glutamatergic activity also increases in the MePD during puberty without a corresponding γ-aminobutyric acid (GABA)ergic change, suggesting an overall activation of this brain region. In the present study, we report that neurotoxic lesioning of the MePD advances puberty and increases weight gain in female rats fed a normal diet. However, MePD lesioned rats fed a 25% nonnutritive bulk diet also showed the dramatic advancement of puberty but without the increase in body weight. In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior. Chronic GABAA receptor antagonism in the MePD from postnatal day 21 for 14 days also advanced puberty, increased socialization, and decreased play fighting without altering body weight, whereas glutamate receptor antagonism delayed puberty and decreased socialization without affecting play fighting. In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake. MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.

Background: In recent years, much attention has been given to the spread of influenza around the world. With the continuing human outbreak of H5N1 beginning in 2003 and the H1N1 pandemic in 2009, focus on influenza and other respiratory viruses has been increased. It has been accepted for decades that international travel via jet aircraft is a major vector for global spread of influenza, and epidemiological differences between tropical and temperate regions observed. Thus we wanted to study how indoor environmental conditions (enclosed locations) in the tropics and winter temperate zones contribute to the aerosol spread of influenza by travelers. To this end, a survey consisting of 632 readings of temperature (T) versus relative humidity (RH) in 389 different enclosed locations air travelers are likely to visit in 8 tropical nations were compared to 102 such readings in 2 Australian cities, including ground transport, hotels, shops, offices and other publicly accessible locations, along with 586 time course readings from aircraft., Results: An influenza transmission risk contour map was developed for T versus RH. Empirical equations were created for estimating: 1. risk relative to temperature and RH, and 2. time parameterized influenza transmission risk. Using the transmission risk contours and equations, transmission risk for each country's locations was compared with influenza reports from the countries. Higher risk enclosed locations in the tropics included new automobile transport, luxury buses, luxury hotels, and bank branches. Most temperate locations were high risk., Conclusion: Environmental control is recommended for public health mitigation focused on higher risk enclosed locations. Public health can make use of the methods developed to track potential vulnerability to aerosol influenza. The methods presented can also be used in influenza modeling. Accounting for differential aerosol transmission using T and RH can potentially explain anomalies of influenza epidemiology in addition to seasonality in temperate climates.

Background: This study attempted to replicate Luminex experimental results for large numbers of beads per classifier using multiplexed assays and routine instrument use conditions., Conclusion: Using larger numbers of microspheres per classifier highlights a fundamental stochastic distribution of bead counts issue complicated by other factors. The more classifiers and the higher the count required per classifier there are, the more apparent the distribution of counts per classifier will be, and the more microspheres are required. Additional problems have been identified. Alternate methods of improving precision and reliability are recommended such as intraplexing and multi-well sample replicates to improve precision and confidence.

Background: Luminex suspension microarray assays are in widespread use. There are issues of variability of assay readings using this technology., Methods and Results: Size variation is demonstrated by transmission electron microscopy. Size variations of microspheres are shown to occur in stepwise increments. A strong correspondence between microsphere size distribution and distribution of fluorescent events from assays is shown. An estimate is made of contribution of microsphere size variation to assay variance., Conclusion: A probable significant cause of variance in suspended microsphere assay results is variation in microsphere diameter. This can potentially be addressed by changes in the manufacturing process. Provision to users of mean size, median size, skew, the number of standard deviations that half the size range represents (sigma multiple), and standard deviation is recommended. Establishing a higher sigma multiple for microsphere production is likely to deliver a significant improvement in precision of raw instrument readings. Further research is recommended on the molecular architecture of microsphere coatings.