bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals
Authors: Churchill Nathan W. , Roudaia Eugenie , Jean Chen J. , Gilboa Asaf , Sekuler Allison , Ji Xiang , Gao Fuqiang , Lin Zhongmin , Masellis Mario , Goubran Maged , Rabin Jennifer S. , Lam Benjamin , Cheng Ivy , Fowler Robert , Heyn Chris , Black Sandra E. , MacIntosh Bradley J. , Graham Simon J. , Schweizer Tom A.
Published: October 2023

Introduction

Post‐acute coronavirus disease 2019 (COVID‐19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long‐term effects of COVID‐19 and post‐COVID headache on brain function remain poorly understood, particularly among non‐hospitalized individuals. This study focused on the power‐law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post‐COVID syndrome, with greatest reductions among those with persistent headache.

Methods

Resting‐state blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID‐19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu‐like symptoms but  tested negative for COVID‐19. Individuals were assessed an average of 4–5 months after COVID testing, in a cross‐sectional, observational study design.

Results

No significant differences in H values were found between non‐headache COVID‐19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non‐headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity.

Conclusions

These findings provide new insights into the neurophysiological mechanisms that underlie persistent post‐COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.
Strategizing green destination image through social media functionality: A study of the tourism industry
Authors: Khatoon Najma , Choudhary Farah
Published: October 2023

This study validates and confirms the multidimensionality of social media functionality in the tourism industry. It also examines the impact of social media functionality on green destination image. Non‐probability convenience sampling technique has been used to collect the data from 550 visitors using a 5‐point Likert scale questionnaire, from the tourists visiting various destinations of Ladakh, India. Results revealed a significant impact of social media functionality on green destination image. The scale of social media functionality was also tested with special reference to the tourism industry. The outcomes of the study deliver insightful outcomes related to the role of social media functionality in developing and maintaining destination image with social media‐based marketing.
Anthocyanins of Hierbamora (Solanum nigrescens): Revealing their Nutraceutical Potential for Controlling Hypertriglyceridemia and Helicobacter pylori Viability
Authors: Pacheco‐Hernández Yesenia , Lozoya‐Gloria Edmundo , Cruz‐Durán Ramiro , Villa‐Ruano Nemesio
Published: October 2023

We present the inhibitory properties of the Solanum nigrescens anthocyanin fraction (SNAF) and its major constituents on alpha‐glucosidase (AG), pancreatic lipase (PL), HMG‐CoA reductase, and ornithine decarboxylase (ODC). The effect of SNAF was simultaneously evaluated in ICR male mice exposed to triglyceride charge test (TCT). HPLC‐MS profiling revealed the presence cyanidin‐3‐O‐rutinoside‐5‐glucoside (CRG), delphinidin‐3‐(p‐coumaroyl)‐rutinoside‐5‐glucoside (DCRG), and petunidin‐3‐(cis‐p‐coumaroyl)‐rutinoside‐5‐glucoside (PCRG) as major constituents of the fraction. SNAF, CRG, and specially PCRG, induced strong non‐competitive inhibition on PL (IC50, 33–86 μg mL−1). The results of TCT confirmed their capacity to ameliorate (p <0.001) hypertriglyceridemia during postprandial and interdigestive stages. SNAF, CRG, DCRG, and PCRG caused negligible growth inhibition (MIC>600 μg mL−1) on beneficial bacteria whereas SNAF and DCRG exerted inhibitory activity on Helicobacter pylori ATCC 53504 (MIC,187‐64 μg mL−1). Additional exploration revealed that SNAF and DCRG produced non‐competitive activity on H. pylori urease, which facilitates bacterial growth under acidic conditions.
Distal radius chondrosarcoma in a 35‐year‐old female patient: A case report
Authors: Sahito Badaruddin , Shah Hussain Haider , Zehra Syeda Alishah , Saquib Javeria , Ahmed Farea , Hussain Muhammad Sheheryar , Dave Tirth
Published: October 2023

Key Clinical Message

Chondrosarcoma, although rare in the distal radius, poses significant challenges. Early diagnosis through incisional biopsy is essential. Surgical resection with margin control and fibular grafting can be effective, but vigilant surveillance is crucial due to its aggressive nature. Metastasis demands consideration of additional interventions or palliative care.

Chondrosarcomas constitute a rarity in the upper limbs, and their occurrence in the distal radius is even rarer with only one case previously documented. We report a case of distal radius chondrosarcoma in a 35‐year‐old female patient who presented with pain and swelling in her left wrist. Following an initial examination, an incisional biopsy was performed, confirming the diagnosis of dedifferentiated chondrosarcoma. The patient underwent a marginal resection of the distal radius and first carpal with ipsilateral fibular and locking compression plate fixation. Unfortunately, despite the interventions, the patient experienced recurrent swelling and ultimately required below‐elbow amputation, followed by above elbow amputation due to metastasis. Unfortunately, the patient passed away due to recurrence and metastasis.
Preserving Timely Generic Drug Competition with Legislation on “Skinny Labeling”
Authors: Tu S. Sean , Kesselheim Aaron S.
Published: October 2023

Patents prevent generic drug entry. Brand firms file new “method of use” patents for old drugs to prevent generic entry. Congress addressed this issue by creating the “skinny label” pathway, which allows generic firms to use the drug label to indicate that the old drug can only be used for non‐patented uses. This pathway is now in jeopardy due to a recent court case. This paper outlines the issues and suggests possible legislative solutions.
A hybrid energy harvesting framework and graphene‐based supercapacitor for 6G and smart grid networks
Authors: Narayanan Vinothini , Govindasamy Ananthi
Published: October 2023

This paper proposes a novel hybrid energy harvesting framework integrated with a graphene‐based supercapacitor to address the energy demands of 6G communication systems and smart grid networks. To ensure consistent power generation, the proposed framework combines diverse energy harvesting mechanisms, including acoustic, vibration, and radio frequency (RF) energy sources. These harvested energies are then efficiently managed and stored in a proposed graphene‐based supercapacitor compared with existing Li‐ion batteries, due to its high energy density and rapid charge‐discharge capabilities. Smart grids and 6G networks can utilize the energy that hybrid systems harvest. This paper examines the analysis of RF energy extracted from various antenna configurations. In the acoustic energy harvesting system, energy extraction has been achieved by subjecting it to acoustic pressure and impedance. Notably, the inclusion of acoustic impedance has resulted in a greater amount of harvested energy. The vibration energy harvesting analysis with angular frequencies under various force conditions is employed. The magnitude of force applied to the harvesting system significantly influences the efficiency of the harvested energy. The three‐dimensional structure and voltage levels of the graphene‐based supercapacitor have been examined for various electrodes. For maximizing the harvested hybrid energy, convex optimization is formulated due to its ability to efficiently navigate complex design spaces while ensuring reliable and globally optimal solutions. CVX tool in MATLAB is used for validation. The results improve the energy harvesting efficiency and enhance the power availability of all the harvesting sources. Furthermore, the compatibility of the proposed framework with existing network infrastructure highlights its potential for seamless integration into real‐world communication and energy distribution systems.
Maternal care behavior and physiology moderate offspring outcomes following gestational exposure to opioids
Authors: Myers Abigail M. , Bowen Scott E. , Brummelte Susanne
Published: October 2023

The opioid epidemic has resulted in a drastic increase in gestational exposure to opioids. Opioid‐dependent pregnant women are typically prescribed medications for opioid use disorders (“MOUD”; e.g., buprenorphine [BUP]) to mitigate the harmful effects of abused opioids. However, the consequences of exposure to synthetic opioids, particularly BUP, during gestation on fetal neurodevelopment and long‐term outcomes are poorly understood. Further, despite the known adverse effects of opioids on maternal care, many preclinical and clinical studies investigating the effects of gestational opioid exposure on offspring outcomes fail to report on maternal care behaviors. Considering that offspring outcomes are heavily dependent upon the quality of maternal care, it is important to evaluate the effects of gestational opioid exposure in the context of the mother−infant dyad. This review compares offspring outcomes after prenatal opioid exposure and after reduced maternal care and integrates this information to potentially identify common underlying mechanisms. We explore whether adverse outcomes after gestational BUP exposure are due to direct effects of opioids in utero, deficits in maternal care, or a combination of both factors. Finally, suggestions for improving preclinical models of prenatal opioid exposure are provided to promote more translational studies that can help to improve clinical outcomes for opioid‐dependent mothers.
Temperature during pupal development affects hoverfly developmental time, adult life span, and wing length
Authors: Daňková Klára , Nicholas Sarah , Nordström Karin
Published: October 2023

Hoverflies (Diptera, Syrphidae) are cosmopolitan, generalist flower visitors and among the most important pollinators after bees and bumblebees. The droneflyEristalis tenaxcan be found in temperate and continental climates across the globe, often synanthropically.Eristalis tenaxpupae of different generations and different climate zones are thus exposed to vastly different temperatures. In many insects, the ambient temperature during the pupal stage affects development, adult size, and survival; however, the effect of developmental temperature on these traits in hoverflies is comparatively poorly understood. We here rearedE.tenaxpupae at different temperatures, from 10°C to 25°C, and quantified the effect on adult hoverflies. We found that pupal rearing at 17°C appeared to be optimal, with high eclosion rates, longer wings, and increased adult longevity. Rearing temperatures above or below this optimum led to decreased eclosion rates, wing size, and adult survival. Similar thermal dependence has been observed in other insects. We found that rearing temperature had no significant effect on locomotor activity, coloration or weight, despite evidence of strong sexual dimorphism for each of these traits. Our findings are important as hoverflies are key pollinators, and understanding the effects of developmental temperature could potentially be useful for horticulture.
Pine marten predation of common goldeneye nests: Effects of cavity age and habitat override any effect of microtine rodent abundance
Authors: Sonerud Geir A. , Grønlien Helge E. , Steen Ronny
Published: October 2023

According to the alternative prey hypothesis (APH), the temporal synchrony in population fluctuations of microtine rodents and other small herbivores in boreal areas is caused by generalist predators with numerical and functional response to microtines, leading to an increased predation of prey alternative to microtines in the low phase of the microtine population fluctuations. The tree‐climbing pine marten (Martes martes) is a food generalist that includes bird eggs among its alternative prey, also eggs of the cavity‐nesting common goldeneye (Bucephala clangula). We used long‐term data to test whether pine marten predation of goldeneye eggs in nest boxes varied as predicted by the APH. As a measure of microtine abundance at the time of nesting, we applied two measures. First, for goldeneye nests located <40 km from our microtine trapping site, we applied the trapping index of microtine rodents. Second, to also use data from nests located >40 km from our microtine trapping site, and from nests in years when trapping was not conducted, we used two proxies for the microtine abundance: whether boreal owls (Aegolius funereus) nested in any of our boxes <40 km from each goldeneye nest and the average clutch size of these boreal owls. The probability of predation of a goldeneye nest was independent of the microtine trapping index and independent of the proxies for microtine abundance. However, it increased with cavity age, taken as the number of nesting seasons elapsed since the actual nest box was installed, and declined with distance from habitat with forest canopy. The effect of cavity age confirms that the long‐term spatial memory of pine marten is an important factor in the pattern of its predation on nests in tree cavities.
Individual consistency in the localised foraging behaviour of shy albatross (Thalassarche cauta)
Authors: Mason Claire , Hobday Alistair J. , Lea Mary‐Anne , Alderman Rachael
Published: October 2023

Quantifying the intra‐ and interindividual variation that exists within a population can provide meaningful insights into a population's vulnerability and response to rapid environmental change. We characterise the foraging behaviour of 308 trips taken by 96 shy albatross (Thalassarche cauta) from Albatross Island across seven consecutive years. At a population level, incubating shy albatross exploited a consistent area within ca. 500 km radius of their breeding colony. During half of the trips, individuals utilised the closest shelf break to the west of the colony, where upwelling events have been reported. The other half of the trips were exclusively within the neritic zone, utilising a variety of locations within the Bass Strait. Furthermore, we found evidence of individual consistency to geographic locations, with subsequent trips by an individual more similar than random trips from all individuals in our data, both within and between years (G‐test, p < .05). Between‐individual variation in foraging behaviour was not meaningfully explained by age (linear regression, p > .05) or sex (t‐test, p > .05) for any metric, suggesting that other intrinsic individual factors are accounting for between‐individual variation in foraging trips. A localised foraging distribution is unusual for albatross, which, combined with high variation in space use between individuals demonstrated here, suggests that this species is accessing adequate resources near the colony. Overall, these findings suggest that incubating shy albatross from Albatross Island exhibit tendencies of a generalist population comprised of uniquely specialised individuals. These results suggest that this species is operating below its biological capacity in this fast‐warming area and provide a baseline from which to assess future change.
Electrochemical Selenylation of Alkynyl Aryl Ketones: Efficient Synthesis of 3‐Selenylated Chromones under Catalyst‐ and Chemical‐Oxidant‐Free Conditions
Authors: Cen Kaili , Wei Jiahao , Liu Yuan , Tan Zhixuan , Wang Xinye , Wang Dahan , He Wei‐Min , Cai Jinhui
Published: October 2023

An electrochemical synthesis of various 3‐selenylated chromones via selenylation of alkynyl aryl ketones without the employment of catalyst and chemical‐oxidant is described here. This method features mild conditions, high efficiency, and wide substrate scope. Furthermore, the scale‐up reaction runs smoothly which indicates the practicability of this electrosynthesis strategy.
MENA oil exporters need a renewable energy transition before the oil wells run dry: A special focus on innovation, financial development, and governance
Authors: Matallah Siham
Published: October 2023

Unlike previous studies, this paper specifically casts light on Middle Eastern and North African (MENA) oil exporters that desperately need to give a strong boost to renewable energy (RE) sources and export rather than uselessly burn their hydrocarbon resources, which support an overwhelming part of their economies. This paper extends the previous research by investigating the impact of oil revenues, innovation, financial development, and governance on renewable energy generation in eight oil‐rich MENA countries over the period 1996–2020 using the three‐stage least squares (3SLS) estimator, which is asymptotically more efficient than the two‐stage least squares (2SLS) employed in the similar‐scoped study of Bellakhal et al. (Energy Economics, 2019, 84, 104541). Furthermore, this study aims to detect structural changes in the econometric relationships between variables depending on a novel test with structural breaks proposed by Karavias and Tzavalis (Computational Statistics & Data Analysis, 2014, 76, 391–407). The main findings indicate that oil rents negatively and significantly affect RE production in MENA oil exporters in general and in non‐GCC countries in particular. While renewable energy production in the GCC countries is positively and significantly affected by oil rents. Innovation‐led RE increases at a greater pace in the GCC countries than in their non‐Gulf counterparts. renewable energy production appears to be positively and significantly affected by financial development and governance in oil‐rich MENA countries.
EEG microstates in early‐to‐middle childhood show associations with age, biological sex, and alpha power
Authors: Hill Aron T. , Bailey Neil W. , Zomorrodi Reza , Hadas Itay , Kirkovski Melissa , Das Sushmit , Lum Jarrad A. G. , Enticott Peter G.
Published: October 2023

Electroencephalographic (EEG) microstates can provide a unique window into the temporal dynamics of large‐scale brain networks across brief (millisecond) timescales. Here, we analysed fundamental temporal features of microstates extracted from the broadband EEG signal in a large (N = 139) cohort of children spanning early‐to‐middle childhood (4–12 years of age). Linear regression models were used to examine if participants' age and biological sex could predict the temporal parameters GEV, duration, coverage, and occurrence, for five microstate classes (A–E) across both eyes‐closed and eyes‐open resting‐state recordings. We further explored associations between these microstate parameters and posterior alpha power after removal of the 1/f‐like aperiodic signal. The microstates obtained from our neurodevelopmental EEG recordings broadly replicated the four canonical microstate classes (A to D) frequently reported in adults, with the addition of the more recently established microstate class E. Biological sex served as a significant predictor in the regression models for four of the five microstate classes (A, C, D, and E). In addition, duration and occurrence for microstate E were both found to be positively associated with age for the eyes‐open recordings, while the temporal parameters of microstates C and E both exhibited associations with alpha band spectral power. Together, these findings highlight the influence of age and sex on large‐scale functional brain networks during early‐to‐middle childhood, extending understanding of neural dynamics across this important period for brain development.
Pharmacodynamic Factors of Antibiotic Efficacy
Authors: Rotschafer John C. , Zabinski Richard A. , Walker Karla J.
Published: October 2023

The primary focus of the pharmaceutical industry in past years has been on developing more potent antibiotics rather than on establishing optimum therapy with currently available agents. Concepts that can be used to tailor patient‐ and pathogen‐specific antimicrobial regimens include concentration‐dependent killing, concentration‐independent killing, and postantibiotic effect. It is possible to administer single daily doses (SDD) of aminoglycosides; however, a fixed SDD regimen cannot meet the goals for therapy in all patients. Instead, it is necessary to consider both pharmacodynamic concepts and pharmacokinetic principles. Even with tailored, patient‐specific regimens, however, limitations exist with antibiotic therapy alone. Immunotherapy, used as an adjunct to antimicrobial therapy, may play a role in improving patient outcomes.
Problems and Dilemmas of Antimicrobial Resistance
Authors: Murray Barbara E.
Published: October 2023

An important obstacle to the long‐term efficacy of an antimicrobial agent is the appearance and spread of resistance to the agent. The fact that many antimicrobials are produced by microorganisms in nature may provide long‐term selective pressure for the emergence of resistance in antibiotic‐producing as well as ‐nonproducing organisms. Indeed, the rapidity with which many resistances have appeared after the introduction of a new antibiotic suggests that these resistance genes were already present somewhere in nature prior to clinical use. In the hospital setting, the most recent worrisome resistance traits to emerge include plasmid‐mediated resistance to imipenem and to third‐generation cephalosporins among nosocomial gram‐negative bacteria, and the acquisition of resistance to vancomycin by enterococci. Methicillin‐resistant staphylococci continue to be a problem and are increasingly resistant to numerous other agents such as rifampin and the newer fluoroquinolones. The most important resistances seen in community‐acquired organisms include β‐lactam resistance in pneumococci and combined ampicillin and chloramphenicol resistance in Haemophilus influenzae. Shigellae resistant to essentially all commonly used oral agents are also a problem, particularly in developing countries. No end is in sight to the problem of antimicrobial resistance, and thus new strategies to prevent infections and control resistant organisms continue to be necessary.
Current Perspectives on Antiretroviral Therapy
Authors: Fletcher Courtney V.
Published: October 2023

Current estimates suggest that at least 1 million persons in the United States are infected with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome. Knowledge of the life cycle of HIV has provided the fundamental information necessary to initiate programs that will identify drugs to treat the infection. Inhibition of reverse transcriptase represents the only strategy of proved clinical value. Three such drugs are available: zidovudine, didanosine, and zalcitabine. Zidovudine is the only proved agent for therapy of asymptomatic HIV infection; and for symptomatic disease, monotherapy with zidovudine must also be regarded as the first‐line approach. For patients who are intolerant, are failing clinically, or have received prior long‐term treatment with zidovudine, monotherapy with didanosine or zalcitabine, or a combination of zidovudine and zalcitabine are alternatives. Progress is being made in the treatment of HIV infection, but the considerable challenge to affect the inexorable progressive nature of HIV disease remains daunting.
Cefepime
Authors: Hardin Thomas C. , Jennings Timothy S.
Published: October 2023

Cefepime is a potent, broad‐spectrum, fourth‐generation cephalosporin with enhanced activity against most gram‐positive aerobic bacterial pathogens and many gram‐negative aerobic bacteria that are resistant to other cephalosporins. The drug's zwitterionic structure contributes to more rapid penetration of gram‐negative bacterial cell membranes, and its low affinity for most type I β‐lactamases leads to significantly reduced enzymatic degradation compared with other cephalosporins. Cefepime has a good toxicity profile, with minor gastrointestinal and central nervous system symptoms being most prevalent. At dosages ranging from 1–2 g every 8–12 hours, it is an alternative option for infections of the lower respiratory tract, urinary tract, and skin and skin structures, as well as febrile episodes in neutropenic patients with cancer, and bacteremia or septicemia in critically ill patients.
An Investigation of the Requirement for Increased LH Secretion During the Compensatory Response in Androgen Secretion After Unilateral Castration of the Adult Rat
Authors: DEBERTIN WERNER J. , POMERANTZ DAVID K.
Published: October 2023

ABSTRACT: The endocrine mechanisms underlying the response to unilateral castration were examined by determining systemic androgen and luteinizing hormone (LH) concentrations, as well as testicular vein androgen at 3,6,12, and 24 hours after sham surgery and castration. Systemic androgen was significantly depressed 3 hours after unilateral castration, but had recovered to concentrations observed in sham operated rats at 6, 12, and 24 hours. The recovery of serum androgen after castration was apparently due to increased testicular secretion of androgen, seen as a significant increase in testicular vein androgen. Systemic concentrations of bioactive and immunoactive LH were significantly increased only at 6 hours after castration. The authors next examined whether the increase in LH was necessary for the compensatory secretion of androgen seen after castration. This was accomplished by examining the response to castration when circulating LH was prevented from changing by suppressing endogenous LH secretion with subcutaneous steroid implants and maintaining circulating LH with subcutaneous osmotic pumps containing ovine LH. The compensatory increase in testicular vein androgen was observed 1 and 7 days after castration in rats bearing sham implants. When circulating LH was prevented from changing by using the combination of steroids and LH, however, compensatory secretion of androgen did not occur 1 and 7 days after castration. These results suggest that: 1) compensation in androgen secretion in response to unilateral castration occurs as early as 6 hours; 2) the increase in LH 6 hours after castration may provide the stimulus for the increase in androgen secretion by the testis at this time; 3) the lack of an increase in testicular vein androgen 1 and 7 days after castration in rats whose endogenous LH is prevented from changing indicates that the change seen 6 hours after castration may be an important component of the short‐and long‐term compensatory response.
The Taurine and Hypotaurine Content of Human Semen
Authors: HOLMES ROSS P. , GOODMAN HAROLD O. , SHIHABI ZAK K. , JAROW JONATHAN P.
Published: October 2023

ABSTRACT: Taurine and hypotaurine levels were measured in human sperm and seminal fluid. Sperm taurine ranged from 17 nmol/mg DNA to 348 nmol/mg DNA, and hypotaurine from 0 nmol/mg DNA to 251 nmol/mg DNA. Seminal fluid contained 319 μmol/L to 1590 μmol/L of taurine, but no detectable hypotaurine. The coefficient of variation in multiple ejaculates from a single man for these components ranged from 12% for hypotaurine to 24% for seminal fluid taurine, indicating a relative constancy in their concentrations. Sperm hypotaurine content was significantly correlated with sperm morphology, sperm relative forward progression, the percentage of motile sperm, and the total number of sperm in the ejaculate. By contrast, sperm taurine content was negatively correlated with these parameters. The mean hypotaurine content of sperm from 8 fertile men was 149 ± 92 nmol/mg DNA, four times higher than that of sperm from 9 infertile men, which was 35 ± 19 nmol/mg DNA (P = 0.011). In contrast, the mean sperm taurine content of the fertile men was lower than that of the infertile men (83 ± 33 nmol/mg DNA versus 168 ± 119 nmol/mg DNA, respectively; P = 0.07). Seminal fluid taurine concentrations, however, were similar for both groups. Hypotaurine, an antioxidant, may play an important role in protecting sperm from reactive oxygen species. Higher concentrations of taurine in the sperm of infertile men suggest that accelerated oxidation of hypotaurine to taurine may accompany the observed decline in other sperm parameters.
The Andrology Laboratory in an Assisted Reproductive Technologies Program
Authors: MULLER CHARLES H.
Published: October 2023

Abstract: Assuring the highest possible quality of care to the patient is the first goal of the andrology laboratory. Quality control and quality assurance as they apply to the andrology laboratory are outlined, and special problems in quality control for sperm function assays are addressed. An example of the patient review process is presented. Quality of care also depends on the ability of the laboratory to perform appropriate tests of sperm function that can diagnose sperm defects, predict success or failure of in vitro fertilization, and lead to rational therapies for sperm dysfunctions. Methods for, and diagnostic value of, sperm swim‐out, enhanced sperm penetration assays, acrosome reaction assessment, motility analysis of capacitating sperm, and sperm—zona binding assays are reviewed. No single test, other than in vitro fertilization itself, is capable of providing a complete diagnosis or a highly accurate prediction. A battery of sperm function tests, arranged in an algorithm, is presented as a theoretically better approach.
Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats
Authors: KLINEFELTER GARY R. , ROBERTS NAOMI L. , SUAREZ JUAN D.
Published: October 2023

Abstract: It was recently demonstrated that the Leydig cell toxicant ethane dimethanesulphonate (EDS) produces multiple effects on the epididymis after a single in vivo exposure. To determine whether any of the perturbations were mediated by a direct action of the compound, we used a novel system for the coculture of epididymal epithelial cells and sperm from the caput epididymidis. This system maintains the morphologic integrity and cell polarity of the epididymal epithelial cells before and during coculture, and the sperm recovered after coculture have intact plasma and acrosomal membranes. In addition, several functions required for epididymal sperm maturation are expressed, including the secretion of protein by the epididymal epithelium, the association of secreted protein with the plasma membrane of cocultured sperm, and the acquisition of progressive motility by cocultured sperm. In vitro exposure of epididymal epithelial cells and sperm to EDS results in a significant decline in protein secretion by the epithelial cells during coculture, and in particular, a dose‐dependent decline in a 36‐ to 38‐kd protein (PI 4.0 to 4.5) and a 34‐ to 36‐kd protein (PI 4.5 to 5.0). Moreover, these and other proteins are not recovered from the sperm membrane of cocultured sperm after EDS treatment. Finally, EDS results in a dose‐dependent decline in the percentage of both motile and progressively motile sperm recovered after coculture compared with that of sperm from untreated co‐cultures. These effects on sperm motility were not observed when sperm were pretreated with EDS and subsequently co‐cultured with untreated epithelial cells. We conclude that EDS alters epididymal sperm maturation by acting directly on the epididymal epithelium to mediate changes in sperm membrane protein, and that this may subsequently alter the development of the progressive motility of sperm.
Direct and Indirect Effects of Murine Interleukin‐2, Gamma Interferon, and Tumor Necrosis Factor on Testosterone Synthesis in Mouse Leydig Cells
Authors: MEIKLE A. WAYNE , DE SOUSA JOSE C. CARDOSO , DACOSTA NICOLAU , BISHOP D. KEITH , SAMLOWSKI WOLFRAM E.
Published: October 2023

Abstract: It was recently observed that treatment of patients with a high dosage of human interleukin (IL‐2) resulted in suppression of plasma concentrations of testosterone. A murine model was developed to assess the direct and indirect effects of murine IL‐2 and the secondarily released cytokines, gamma interferon (INFγ), and tumor necrosis factor (TNFα), on testosterone production in isolated Leydig cells. Pretreatment for 24 hours with IL‐2 (100 to 500 IU/ml) or INFγ (100 to 1000 IU/ml) significantly decreased testosterone production in response to luteinizing hormone (LH; P < 0.02 and 0.005, respectively). The combinations of INFγ with either TNFα or IL‐2 produced enhanced suppressive effects on Leydig cell testosterone production. Steroidogenic precursors (22‐hydroxycholesterol, 17α‐hydroxypregnenolone, and dehydroepiandrosterone) restored testosterone secretion to control levels after preincubation with INFγ or TNFα. In contrast, the inhibition of testosterone synthesis produced by either IL‐2 or INFγ plus TNFα could be reversed by 17α‐hydroxypregnenolone and dehydroepiandrosterone, but not by 22‐hydroxycholesterol (P < 0.01). Dibutryl cyclic adenosine monophosphate was also ineffective in reversing the inhibitory effects of these cytokines on synthesis. Although IL‐2 directly inhibited synthesis in isolated Leydig cells, it stimulated testosterone production (P < 0.005) in minced murine testes. This suggests that IL‐2 releases regulatory factors from other cells that were able to overcome the direct inhibitory effect of IL‐2. This stimulatory effect was not caused by INFγ and TNFα because INFγ alone or with TNFα inhibited (P < 0.005) testosterone production in minced testes. These results suggest that INFγ inhibits production by affecting LH‐stimulated events occurring before cholesterol side‐chain cleavage. IL‐2 and the combined effect of INFγ and TNFα additionally inhibit the cholesterol side‐chain cleavage enzyme.
Can Spermatogenesis Be Maintained Quantitatively in Intact Adult Rats with Exogenously Administered Dihydrotestosterone?
Authors: CHEN HAOLIN , CHANDRASHEKAR VARADARAJ , ZIRKIN BARRY R.
Published: October 2023

ABSTRACT: It is well established that testosterone (T) is required to maintain spermatogenesis in the mammalian testis, presumably acting through a receptor mechanism, as elsewhere. It is puzzling, however, that the T concentration that is required to maintain spermatogenesis quantitatively in intact adult rats (15–20 ng/ml) is well in excess of the concentration required to saturate testicular androgen receptors. If, indeed, T regulation of spermatogenesis is mediated through the androgen receptor, 5α‐dihydrotestosterone (DHT) would be expected to more effectively maintain spermatogenesis than T because of its greater affinity for, and slower rate of dissociation from, the androgen receptor. To test this hypothesis experimentally, the quantitative relationship between the intratesticular concentration of exogenously administered DHT and the maintenance of germ cell production was examined in intact rats in which endogenous T production was suppressed. To this end, rats received increasing doses of DHT via polydimethylsiloxane implants of 6–36 cm in length for 8 weeks. In each DHT‐treated rat, serum luteinizing hormone (LH) concentration was reduced to below the limit of detectability by radioimmunoassay (RIA), and intratesticular T concentration was reduced by >90%. Serum and intratesticular DHT concentrations increased with increasing implant size. The serum and intratesticular concentrations of 5α‐androstane‐3α, 17β‐diol (3α‐Diol) were consistently higher than DHT concentrations because of conversion of DHT to 3α‐Diol. Spermatogenesis was maintained qualitatively in some rats that received implants of 6 cm, in most rats that received implants of 12 cm, and in all rats that received implants of 18 cm. Spermatogenesis was maintained quantitatively in most rats that received implants of 24 cm and 36 cm. The minimal average intratesticular concentration of DHT associated with the quantitative maintenance of spermatogenesis was approximately 50% of the T concentration shown previously to be minimally required. These results indicate that DHT, with its greater affinity for, and slower rate of dissociation from, the androgen receptor, more effectively maintains spermatogenesis than T at comparable intratesticular concentrations.
Involvement of Vasoactive Intestinal Peptide (VIP) as a Humoral Mediator of Penile Erectile Function in the Dog
Authors: AOKI HIKARU , MATSUZAKA JUNICHI , YEH KANG‐HSIUNG , SATO FUMIO , FUJIOKA TOMOAKI , KUBO TAKASHI , OHHORI TSUTOMU , YASUDA NAOKI
Published: October 2023

ABSTRACT: The effects of intracorporeal infusion of anti‐vasoactive intestinal peptide (anti‐VIP) antisera on electrically induced penile erection were studied in 18 male mongrel dogs. Electrical pulse stimulation (4 V, 4 milliseconds, 40 Hz) of the pelvic splanchnic nerve consistently produced penile erection (“electroerection”). Using this erection model, effects of anti‐VIP serum were evaluated with regard to the peak intracorporeal pressure during electroerection. Pretreatment of the animals with repetitive intracorporeal infusion of anti‐VIP rabbit serum completely abolished the electroerection in nine dogs, partially suppressed it (P < 0.01) in five, and was without effects in four. In contrast, control treatment of the same 18 dogs with normal rabbit serum was totally ineffective. In six dogs in which anti‐VIP serum failed to produce a complete suppression of electroerection, 0.5 mg atropine sulfate was additionally given i.v. All six dogs exhibited significant (P < 0.01) suppression of the peak intracorporeal pressure after atropine. However atropine alone did not affect the intracorporeal pressure to any significant degree. To five of these six dogs with positive response to the combination treatment with anti‐VIP serum and atropine, prazosin HCI was added i.v. It was found that prazosin HCI reversed the attenuation of electroerection produced by combined anti‐VIP serum and atropine. Prazosin did not affect the intracorporeal pressure when administered following anti‐VIP serum. These results suggest that VIP plays a role as a humoral mediator involved in penile erection and that there is a synergistic interaction between VIP and acetylcholine. Also it appears that the effect of acetylcholine but not that of VIP is mediated by the alpha‐1 adrenergic mechanism.
Semen of Spinal Cord Injured Men Freezes Reliably
Authors: PADRON OSVALDO F. , BRACKETT NANCY L. , WEIZMAN MICHAEL S. , LYNNE CHARLES M.
Published: October 2023

ABSTRACT: The objectives of the present study were to: 1) determine the effect of cryopreservation on the percent and the grade of motility of sperm from spinal cord injured (SCI) men and 2) determine which method of freezing yields the best post‐thaw motility in sperm from SCI men. Antegrade semen samples were obtained from 9 SCI subjects and 10 age‐matched healthy control subjects. Motility in fresh samples was determined and cryopreservative medium was added to each sample. Aliquots of each sample were frozen according to three methods: 1) liquid nitrogen vapor only (V); 2) vapor for 12 minutes followed by submersion into liquid nitrogen (V+N2); and 3) direct submersion into liquid nitrogen (N2). Samples were frozen for 1 week, then thawed. The post‐thaw percent and grade of motility was determined. The mean percent motility of fresh samples for SCI subjects (21.0%) was significantly lower than that for control subjects (55.7%). After thawing, the mean percent drop in motility for V, V+N2, and N2 for controls was 65.2%, 73.5%, and 79.4%, respectively, and for SCI subjects, it was 64.7%, 74.5%, and 81.6%, respectively. There was no statistically significant difference between control and SCI subjects by method of freezing. Vapor only as a freezing method was superior to all other methods for retention of sperm motility in both control and SCI subjects. We conclude that the semen of SCI men may be frozen reliably and that their sperm retain motility similar to that of normal men. Vapor only, being the most gentle method used, gives the best recovery of sperm motility in either group.
Comparative Study of Experimentally Induced Benign and Atypical Hyperplasia in the Ventral Prostate of Different Sat Strains
Authors: SCOLNIK MARISA D. , SERVADIO CIRO , ABRAMOVICI ARMAND
Published: October 2023

ABSTRACT: The induction of prostatic lesions in the rat by hormonal manipulation and/or chemical carcinogens in different strains is well documented in literature. However, the selection of a strain for such studies was merely based on the laboratory husbandry facilities rather than on the animal genotype. It is well accepted that the morphology and function of the prostate exhibit a marked species‐specific difference that makes extrapolation to other animals and man difficult.

Our group has developed an experimental model for the study of rat prostatic hyperplasia and/or dysplasia induced by citral—a flavor constituent. Previous observations have revealed that the Wistar rat ventral prostate is reactive to citral, especially during its adolescent growth period as well as during the redifferentiation stage among postcastrated rats treated with exogenous testosterone. The present study presents data on the ventral prostate susceptibility of three additional strains selected by their interrelated endocrine morbidity. In order to facilitate an objective comparative analysis of the prostatic lesions a histopathological score chart was elaborated. The present findings showed that the Wistar and Sprague‐Dawley strains were the most susceptible to developing benign and atypical prostatic hyperplasia both in intact and postcastrated rats. The F344 and ACI/Ztm rat strains remained refractory toward all of these treatments. Our data provide evidence that the strain genotype and, more precisely, their endocrine background, play a determinative role in the prostatic responsiveness towards citral. It is suggested that additional consideration be given to the selection of an adequate animal strain when studying experimental neoplastic transformation, especially when hormonal interactions might be involved.
Effect of Finasteride on Adrenal Steroidogenesis in Men
Authors: RITTMASTER ROGER S. , ANTONIAN LIDA , NEW MARIA I. , STONER ELIZABETH
Published: October 2023

ABSTRACT: Finasteride, a 5α‐reductase inhibitor, does not bind to the androgen receptor and has no other known hormonal activity. To determine what effect, if any, it has on adrenal steroidogenesis, 10 healthy men received 5 mg finasteride daily for 28 days. Adrenocorticotropic hormone (ACTH) stimulation tests were performed before and after 4 weeks of finasteride administration (5 mg daily). Serum levels of 17‐hydroxypregnenolone, 17‐hydroxyprogesterone, deoxycorticosterone, corticosterone, aldosterone, Cortisol, dehydroepiandrosterone, and androstenedione were measured before and 60 minutes after i.v. ACTH. Finasteride decreased serum dihydrotestosterone levels from 31 ± 5 to 4.4 ± 1.2 ng/dl (P < 0.001). There were no significant changes in basal or ACTH‐stimulated serum levels of adrenal steroids. There was also no significant decrease in the product to precursor ratio for the seven adrenal enzymes tested. Finasteride increased mean serum androstenedione levels by 17% (P = 0.10) and significantly increased the androstenedione to 17‐hydroxyprogesterone ratio (P = 0.02 before ACTH and 0.05 after ACTH). These changes are most likely due to inhibition of androstenedione metabolism by 5α‐reductase. In conclusion, finasteride has no detectable effect on adrenal steroidogenesis, other than that which can be explained by inhibition of the 5α‐reductase enzyme.
Nanovid Microscopy for Assessing Sperm Membrane Changes Induced by In Vitro Capacitating and Acrosomal Reacting Procedures
Authors: Degelos Suzanne D. , Wilson Michael P. , Chandler John E.
Published: October 2023

ABSTRACT: This study was to verify the usefulness of Nanovid microscopy techniques for evaluating induced modifications in bovine spermatozoal membranes. Frozen thawed bovine sperm were labeled with 20‐nm colloidal gold particles bound to concanavalin A (ConA) or heparin ligands. Sperm membrane changes were induced in vitro by capacitating and acrosome‐reacting procedures. Capacitatton was induced by incubation with 10 μg/ml of heparin for 4 hours at 37°C, 5% CO2, and high humidity. Membrane changes associated with the acrosome reaction were induced by addition of lysophosphatidyicholine (100 μg/ml) and incubation for 15 minutes at 37°C, 5% CO2, and high humidity. Gray intensity (black = 0; white = 255) of sperm (ONCELL) and background (OFFCELL) were evaluated with computer‐enhanced videomicroscopy with either differential interference contrast (DIC) or Nanovid optics. A high gold concentration on a membrane region produced blacker video pictures with Nanovid microscopy. Gray intensity of video pictures of a region with little or no gold would have a gray intensity equal to or greater than that of the background, that is, toward white. Weighted least squares methods were used to analyze ONCELL data using OFFCELL as a covariate. In experiment 1, ONCELL intensities of cells labeled with ConA‐gold complex were lower than those labeled with heparin‐gold at the same treatment level. In experiment 2, ONCELL intensity decreased as the concentration of heparin—gold increased from 0 to 0.041 μg/μl heparin. ONCELL intensity significantly de‐creased after sperm were treated with the highest heparin‐gold level and acrosome reacted. Differences in ONCELL intensity of acrosome‐reacted sperm were smaller in experiment 1 than in experiment 2. Nanovid microscopy techniques resulted in lower ONCELL intensities than did DIC microscopy in both experiments.
Post‐Thaw Bovine Spermatozoal Quality Estimated from Fresh Samples
Authors: THOMAS C. A. , GARNER D. L.
Published: October 2023

ABSTRACT: Comparisons were made among flow cytometrically quantified populations of fresh and cryopreserved bovine spermatozoa, tri‐stained with fluorophores rhodamine 123 (R123), 5‐ (and 6‐) carboxy‐4′,5′‐dimethytfluorescein diacetate (CMFDA), and propidium iodide (PI), and analyzed by dual parameter flow cytometry. The purpose was to find parameters in fresh semen samples that were potentially predictive of frozen sample parameters so that bulls with marginal cryopreservation capacity could be identified. Fresh and cryopreserved aliquots of semen from two sets of six bulls were semen processed in either milk (bulls 1–6) or egg yolk citrate (bulls 11–16). Membrane‐damaged red (PI) and intact green (CMFDA + R123) populations were evaluated as percentages of 10,000‐cell samples or numbers per straw. In milk, gated central subsets of membrane‐damaged sperm cells in fresh samples and moribund cells in post‐thaw samples were significantly correlated for sample percentages (r=0.90, P=0.014) and cell numbers per straw (r=0.94, P=0.006). In egg yolk citrate, fresh and frozen membrane‐damaged populations were correlated (percentages: r = 0.81, P = 0.048; numbers: r = 0.88, P = 0.019). Additionally, post‐thaw motility estimated by a photographic method was correlated with the number of sperm cells per straw in the intact central green subset (r = 0.98, P= 0.0006). These findings suggest that partitioning red and green populations into smaller, central subset populations reveals significant relationships between fresh and cryopreserved bull ejaculates. The proportion of membrane‐damaged spermatozoa in fresh semen seems to be predictive of the proportion of post‐thaw membrane‐damaged or moribund spermatozoa. The data consistently showed ejaculates of bulls 1 and 12 as having the greatest cryopreservation potentials, and bulls 4 and 16 the least. Thus, flow cytometric evaluation of fresh semen may be useful for identifying young sires with relatively poor fertilizing potential.