bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between activity in the ventral premotor cortex and spinal cord activation during force generation—A combined cortico‐spinal fMRI study
Authors: Braaß Hanna , Feldheim Jan , Chu Ying , Tinnermann Alexandra , Finsterbusch Jürgen , Büchel Christian , Schulz Robert , Gerloff Christian
Published: October 2023

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is associated with the activity in the cerebral primary motor and premotor areas is poorly understood. Here, we conducted combined cortico‐spinal functional magnetic resonance imaging during a simple visually guided isometric force generation task in 20 healthy young subjects. Activation was localized in the right cervical spinal cord and left primary motor and premotor areas. The main finding is that spinal activation was negatively correlated with ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation, while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding that extends our understanding of human motor function beyond the animal literature.
The Antioxidant Vitamins: Impact on Atherosclerosis
Authors: Meyers David G. , Maloley Pierre A.
Published: October 2023

Atherosclerosis, the great killer of Western society, probably is initiated when the balance of subendothelial lipoproteins and oxidation potential is upset. Oxidation products, especially oxidized low‐density lipoprotein, set into motion the cascading of numerous pathways, culminating in the fibrous atherosclerotic plaque. The natural antioxidant system includes enzymes and vitamins A, E, and C. The lipophilic vitamins A and E protect the fatty acid components of lipoproteins and membranes, and vitamin C functions in the aqueous phase both directly and by regenerating oxidized vitamin E. In animal models, the antioxidant vitamins protect lipids and prevent atherosclerosis. Population studies suggest an inverse relationship between atherosclerosis and vitamin levels. Several observational studies and some clinical trials have demonstrated that antioxidant vitamin supplements may prevent atherosclerosis. Although approximately 20% of the United States population regularly consumes vitamin supplements, often in high doses, the antiatherogenic benefits of antioxidant vitamins remain unproved by clinical trials, and the long‐term effects of megadose vitamins are yet undefined.
Reassessing the Therapeutic Range for Theophylline on Laboratory Report Forms: The Importance of 5–15 μg/ml
Authors: Self Timothy H. , Heilker Greta M. , Alloway Rita R. , Kelso Tiffany M. , Abou‐Shala Nabil
Published: October 2023

The therapeutic status of theophylline has changed dramatically over the last decade. As part of this change, a different view of the most appropriate therapeutic range for serum theophylline concentration (STC) has emerged. The National Institutes of Health Expert Panel Report, “Guidelines for the Diagnosis and Management of Asthma,” suggests a conservative approach of aiming for STC of 5–15 μg/ml. This truly landmark document along with several studies in the literature, recently prompted us to change our hospital's laboratory report form for the medical record to read that the therapeutic rage for STC is 5–15 μg/ml. We encourage hospital laboratories or other clinical laboratories who have not already made this change to do so.
Trimethoprim‐Sulfamethoxazole Pharmacokinetics in Trauma Patients
Authors: Hess Mary M. , Boucher Bradley A. , Laizure S. Casey , Stevens Robert C. , Sanders Paula L. , Janning Stephen W. , Croce Martin A. , Fabian Timothy C.
Published: October 2023

Study Objectives. To characterize the pharmacokinetic profile of trimethoprim‐sulfamethoxazole (TMP‐SMX) in trauma patients and to compare these parameter estimates with those obtained in nontrauma patients.

Design. Open‐label, multidose, pharmacokinetic study.

Setting. Trauma intensive care unit of a level 1 trauma center located within a regional medical center.

Patients. Fifteen adult trauma patients with serious gram‐negative infections. All patients were studied on day 1 of treatment, nine on day 3, three on day 5, and two on day 7. One patient was discontinued from the study because of a possible drug‐induced rash.

Interventions. Study patients received TMP 4 mg/kg and SMX 20 mg/kg intravenously every 12 hours. Serial blood sampling was performed up to 4 times per patient between treatment days 1 and 7. Serum was assayed for TMP‐SMX using high‐performance liquid chromatography. A one‐compartment model was fit to the data using maximum likelihood estimation.

Measurements and Main Results. Mean (SD) baseline parameter estimates for TMP were volume 2.1 (0.65) L/kg, half‐life 9.7 (3.0) hours, and clearance 2.6 (0.80) ml/min/kg. Estimates for SMX were volume 0.51 (0.10) L/kg, half‐life 7.8 (2.0) hours, and clearance 0.80 (0.29) ml/min/kg. Both volume (p<0.01) and clearance (p<0.001) for SMX were significantly higher and half‐life (p<0.05) significantly shorter than previously reported estimates in nontrauma patients. No significant differences in TMP parameter estimates were found. Neither TMP nor SMX clearance was significantly correlated with estimated creatinine clearance (p>0.05).

Conclusion. The results indicate that the pharmacokinetics of SMX in trauma patients differ significantly from nontrauma patients, which may result in lower than expected concentrations using standard dosing guidelines.
Ambulatory Pharmacy Services Affiliated With Acute Care Hospitals
Authors: Raehl Cynthia L. , Bond C. A. , Pitterle Michael E.
Published: October 2023

The extent to which hospital‐based pharmacists provide ambulatory clinical pharmacy services in the United States is unknown. We evaluated pharmacists' activities in hospital‐affiliated ambulatory clinics and home health services. A questionnaire was mailed to directors of pharmacy in one‐half of the United States acute care general medical‐surgical hospitals with 50 or more licensed beds. The survey response rate was 56% (n=1174). In 19% of hospitals, pharmacists provided patient care (nondispensing activities) in ambulatory clinics. The most common clinics with pharmacist involvement were diabetes (10% of hospitals), oncology (9%), cardiology (6%), and geriatrics, infectious disease, and pain (4% each). Nondispensing roles varied by clinic type; prescribing by protocol was performed in 57% of anticoagulation clinics and 7% of diabetes clinics. Home health care services, with pharmacists' activity extending beyond providing drugs, were offered by 28% of the hospitals. Thirty‐six percent of the hospitals operated one or more outpatient pharmacies. A statistically significant association was observed between hospitals' inpatient clinical pharmacy services (as assessed by the pharmaceutical care index) and the involvement of pharmacists in both ambulatory clinics and home health care services.
Recombinant Interleukin‐2
Authors: Bruton Jill K. , Koeller Jim M.
Published: October 2023

Recombinant interleukin (IL)‐2 is a newly approved immunoregulatory protein produced by lymphocytes that exhibits a wide range of immunologic effects. It is a true biologic response modifier in that is has no known direct antitumor activity, but mediates its cytotoxicity through activation of effector cells including T cells, natural killer cells, and lymphokine‐activated killer cells. Recombinant IL‐2 has demonstrated activity in patients with renal cell carcinoma and melanoma, with objective response rates of approximately 15–20%. The median duration of response in renal cell carcinoma is 23 months. Toxicity experienced with high‐dose IL‐2 can be significant. The most common dose‐limiting toxicities are hypertension, weight gain, oliguria, respiratory insufficiency, and neurotoxicity. These effects are generally manageable and reversible on discontinuation of therapy. Administration of low‐dose IL‐2 has emerged as a means of substantially reducing toxicity. At least in renal cell carcinoma, it appears that the response rate to low‐dose IL‐2 is comparable to that with higher dosages.
Prolonged, But Not Diminished, Zidovudine Absorption Induced by a High‐Fat Breakfast
Authors: Shelton Mark J. , Portmore Amy , Blum M. Robert , Sadler Brian M. , Reichman Richard C. , Morse Gene D.
Published: October 2023

Study Objective. To determine the effect of a high‐fat breakfast on single‐dose, zidovudine (ZDV) pharmacokinetics.

Design. Open‐label, randomized, crossover study.

Patients. Eighteen asymptomatic subjects (12 men, 6 women) infected with the human immunodeficiency virus (mean CD4 cell counts of 512 ± 178/mm3).

Interventions. Subjects received single 100‐mg oral doses of ZDV as follows: after an 8‐hour fast (treatment A), with a high‐fat breakfast (treatment B), and 3 hours after a high‐fat breakfast (treatment C).

Measurements and Main Results. The high‐fat breakfast significantly reduced the mean (coefficient of variation) maximum plasma concentration (Cmax) from 806 (55%) ng/ml with treatment A to 341 (47%) and 424 (42%) ng/ml with treatments B and C, respectively. The time to Cmax was significantly prolonged from 0.68 (30%) hours with treatment A to 1.7 (54%) and 1.3 (42%) hours with treatments B and C, respectively. Area under the plasma ZDV concentration‐time curve (AUC) was not statistically different across the study treatments. Men had significantly lower (35%) renal clearances of both ZDV and its glucuronide metabolite than women.

Conclusions. When ZDV was given either with or 3 hours after a high‐fat breakfast, its absorption was prolonged and Cmax was reduced relative to fasting. However, systemic exposure, as indicated by AUC, was unchanged. (Pharmacotherapy 1994;14(6):671–677)
Human Interleukin‐1α Crosses the Blood—Testis Barriers of the Mouse
Authors: BANKS WILLIAM A. , KASTIN ABBA J.
Published: October 2023

ABSTRACT: Interleukin‐1α (IL‐1α) has been shown to have direct effects on the gonads, affecting steroidal secretion, DNA synthesis by spermatogonia, and the immune function of the testes. It is unclear, however, how IL‐1α exerts these effects because the testis is partitioned into basal and adluminal compartments by both a vascular and a Sertoli cell barrier. The authors used a highly sensitive method to quantify the unidirectional flux rates (Ki) into the testis of technetium pertechnetate‐labeled human albumin (T‐alb), a compound that does not readily cross the vascular barrier, and human IL‐1α radioactively labeled with 125I (I‐IL). The entry rate (Ki) was almost six times greater for I‐IL than for T‐alb. Part of the enhanced entry of I‐IL was due to a saturable transport system. Nearly 0.2% of the total injection had entered the testes 60 minutes after intravenous administration, and more than 75% of that amount was not accounted for by the albumin space. Collection of testicular interstitial fluid from the basal compartment and seminiferous tubule fluid from the adluminal compartment showed preferential entry of I‐IL into these compartments. Analysis by high‐pressure liquid chromatography of radioactivity recovered from the testis showed that intact I‐IL was entering the testis. The leakiness of the blood‐testis barrier was measured by the rate of entry for T‐alb, which was not altered by injection of unlabeled human IL‐1α in doses of up to 50 μg/kg (5 × 106 U/kg), and by the wet weight of the testes. The results show that circulating IL‐1α can have direct access to the testis, supporting previous studies suggesting a direct effect of IL‐1α on gonadal function.
Reactive oxygen species and human spermatozoa.
Authors: DE LAMIRANDE EVE , GAGNON CLAUDE
Published: October 2023

Abstract: Under moderate conditions, reactive oxygen species (ROS) have been shown to inhibit sperm motility after several hours of incubation. The rapid decrease in flagellar beat frequency observed within the first hour of contact between ROS and spermatozoa was associated with a rapid loss of intracellular adenosine triphosphate (ATP). Motility of intact spermatozoa ceased when their ATP concentration was reduced by 85 ±‐ 5%. Axonemal damage was confirmed when ROS‐treated spermatozoa could not reactivate motility after demembranation in a medium containing magnesium adenosine triphosphate (Mg.ATP). However, in conditions allowing rephosphorylation of the axonemes (addition of cyclic adenosine monophosphate, or cAMP, and protein kinase or sperm extracts to the demembranation medium), the motility could reactivate. Three lines of evidence suggested that ATP depletion induced by ROS treatment was responsible for the effects observed in spermatozoa. First, the rapid decrease in intracellular ATP observed after ROS treatment was closely followed by a decrease in beat frequency, loss of intact sperm motility, and axonemal damage due to insufficient phosphorylation. Second, incubation of spermatozoa with the combination pyruvate‐lactate allowed maintenance of sperm ATP at a normal level and prevented the effects of ROS; furthermore, spermatozoa immobilized after ROS treatment, then supplemented with pyruvate‐lactate, were able to reinitiate motility in parallel with an increase in their ATP level. Third, treatment of spermatozoa with rotenone, an ATP depleting agent, produced effects similar to ROS treatment and could also be reversed by the addition of pyruvate‐lactate. These data are consistent with the conclusion that ROS treatment produced axonemal damage mostly as a result of ATP depletion However, other mechanisms, such as inhibition of sperm protein kinases, are probably involved.
Initiation of Sperm Motility after Mating in the Rat and Hamster
Authors: BEDFORD J. MICHAEL , YANAGIMACHI RYUZO
Published: October 2023

Abstract: Unlike those of many mammals, rat and hamster spermatozoa do not appear to be fully activated at ejaculation. Most rat spermatozoa transported en masse to the uterus approximately 2 minutes after coitus were vigorously motile on recovery soon thereafter in uterine fluid, whereas a majority, and sometimes all, were immotile in samples collected less than 2 minutes after coitus from the anterior vagina of normal females and up to 15 minutes after coitus from the anterior vagina in females with obstructed cervices. Many of these immotile rat vaginal spermatozoa began instant vigorous movement upon exposure to Tyrode's solution or uterine fluid. Hamster spermatozoa recovered from the vagina about 2 minutes after coitus were also immotile or displayed only slow, languid serpentine movements, but that motility profile remained very similar in spermatozoa taken 0.5 hours to 6 hours after coitus from the uterus, which is essentially fluid‐free in the hamster. In the hamster, actively motile spermatozoa were evident only in the isthmus of the (transilluminated) oviduct. As in the rat, immotile vaginal and uterine hamster spermatozoa instantly began vigorous progressive motility in vitro on contact with Tyrode's solution or rat uterine fluid. Immotile spermatozoa from the rat and hamster cauda epididymidis immediately became highly motile in Tyrode's solution, and they developed a somewhat less rapid flagellar beat in 150 mmol/L NaCI or KCI, with or without 2mmol/L CaCI2. In contrast, dilution with an isotonic sucrose solution containing no ions, or only 2mmol/L CaCI2, evoked very slow and transient movement of rat and hamster epididymal sperm tails. We conclude that uterine fluid is a primary activating agent of sperm motility in the rat, whereas in the hamster active motility first develops only in the oviduct. The motility initiation factors in the female reproductive tract of the rat and hamster appear to be nonspecific. In vitro observations confirm that, although dilution of epididymal immobilin in which spermatozoa are enmeshed may play some minor part in initiating motility, other elements, including monovalent cations, are the major stimulus for the initiation of epididymal sperm motility in these species.
Antioxidant Enzyme Activity in the Maturing Rat Testis
Authors: PELTOLA VILLE , HUHTANIEMI ILPO , AHOTUPA MARKKU
Published: October 2023

Abstract: Developmental profiles of the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH‐Px), glutathione transferase (GSH‐Tr), and hexose monophosphate shunt (HMS) were measured in the rat testis and liver. The level of SOD in the testis was high at the age of 6 to 10 days, after which it dropped to approximately one third of that level by 20 days of age, and remained there up to 8 months of age. In the liver, SOD activity steadily increased from the neonatal to adult stage of life, reaching the same level as detected in the testis. The testicular activity of catalase was only 2% to 7% of that found in liver at all ages. It increased in both organs up to 6 weeks of age, whereafter the hepatic activity gradually decreased and no further changes were seen in the testis. The GSH‐Px activity was low in the testis and declined slightly with age, whereas activity in the liver increased four‐fold between birth and adulthood. The activity of GSH‐Tr was similar in both organs studied: it increased after birth, showing a maximum in the liver at 1.5 months (ten‐fold increase) and in the testis at 5 months of age (four‐fold increase). The HMS activity was two to three times higher in the liver than in the testis, and decreased slightly with age in both organs. Thus, the basal levels and developmental profiles of antioxidant enzymes in the testis differ greatly from those in the liver. The very high ratio of SOD to catalase plus GSH‐Px in testis (0.92 to 3.48), compared with that found in the liver (0.009 to 0.083), makes the former especially vulnerable to the harmful effects of reactive oxygen species. The peak in SOD activity at 6 to 10 days of age might be related to the physiologic events leading to cell differentiation at this time.
DNA Organization in Human Spermatozoa
Authors: BARONE JOS EPH G. , de LARA JOCELYN , CUMMINGS KENNETH B. , WARD W. STEVEN
Published: October 2023

ABSTRACT: Previous studies from this laboratory on hamster spermatozoa have demonstrated that rodent sperm DNA is packaged into the sperm nucleus in a specific manner by nuclear structures. The entire genome is organized into DNA loop domains attached at their bases to a sperm nuclear matrix, the skeletal structure of the nucleus. When nuclei are completely decondensed, the nuclear matrix dissipates, and the entire genome remains anchored to a single structure located at the base of the tail, termed the nuclear annulus. Here, we have extended these studies to human sperm nuclei, which were found to be similar to hamster. Human sperm DNA was found to be organized into loop domains attached at their bases to a nuclear matrix. The average size of the human sperm halo of DNA surrounding the extracted sperm nucleus (made up of DNA loop domains) was about 50% smaller than those that have been reported for somatic cells (this corresponds to an approximate loop domain size of 26.8 ± 2.1 kb). Human sperm DNA also remained anchored to the base of the tail when completely decondensed, indicating the existence of a nuclear annulus‐like structure in human spermatozoa; but, unlike the hamster nuclear annulus, the human annulus could not be isolated because of its structural instability when separated from the tail. Using human centromere repeats as a probe for in situ hybridization, we examined the packaging of individual DNA sequences within the sperm nucleus. These studies demonstrate that human sperm DNA is highly organized by nuclear structures.
Stimulation of Cryopreserved Epididymal Spermatozoa of the Domestic Cat Using the Motility Stimulants Caffeine, Pentoxifylline, and 2‘‐Deoxyadenosine
Authors: STACHECKI JAMES J. , GINSBURG KENNETH A. , ARMANT D. RANDALL
Published: October 2023

ABSTRACT: We have investigated the effects of caffeine, pentoxifylline, and 2′‐deoxyadenosine on the motion characteristics and longevity of domestic cat spermatozoa. Freshly collected or cryopreserved domestic cat epididymal sperm were incubated with 0.01–20 mM caffeine, pentoxifylline, or 2′‐deoxyadenosine for 15 minutes at 23°C. The percent motility (MOT), curvilinear velocity (VCL), linearity (LIN), straight line velocity (VSL), and amplitude of lateral head displacement (ALH) were determined for each group using computer‐assisted semen analysis. Freshly collected domestic cat sperm exhibited a strong forward progressive movement, and treatment with caffeine, pentoxifylline, or 2′‐deoxyadenosine did not consistently alter sperm motion. Following cryopreservation, spermatozoa exhibited decreased (P < 0.05) MOT, VCL, VSL, and ALH. Caffeine and pentoxifylline increased (P < 0.05) the MOT, VSL, VCL, and ALH of cryopreserved sperm at 0.01–20 mM, in a dose‐dependent manner. 2′‐Deoxyadenosine also increased (P < 0.05) both VSL and VCL at 1.0 mM, and MOT, VSL, VCL, and ALH at 10 mM. All treatments shifted the percentage of nonhyperactive sperm to either a transitional or hyperactivated state. The motility indices of cryopreserved samples were examined during a 6‐ hour incubation to assess the effects of caffeine, pentoxifylline, and 2′‐deoxyadenosine on sperm longevity. Compared to untreated control samples, the longevity of stimulated cryopreserved sperm was not reduced. These results indicate that motility stimulants may prove useful for enhancing the fertility of cryopreserved cat sperm by increasing their motility and producing hyperactivated motion.
Thanatogen Expression During Involution of the Rat Ventral Prostate After Castration
Authors: GUENETTE R. SEAN , DAEHLIN LARS , MOOIBROEK MARILYN , WONG KIM , TENNISWOOD MARTIN
Published: October 2023

ABSTRACT: After castration the rat ventral prostate undergoes regression. This process occurs due to the induction of apoptosis, or active cell death, in the epithelial cells of the gland. Several genes, including TRPM‐2, (testosterone repressed prostate message), RVP. 1, fos, and myc, have been shown to be induced in the prostate during this process. We have investigated the expression of several other genes that may be associated with apoptosis, including tissue transglutaminase (TGase), poly(ADP)ribose polymerase (PARP), and heat shock protein 27 (Hsp27). Northern hybridization has been used to determine the steady‐state mRNA levels of these genes in the ventral prostate after castration, and the time course of induction has been compared to the changes in the steady‐state levels of prostate steroid binding protein (PSBP), α‐tubulin, and TRPM‐2 mRNAs. The results show that the mRNAs for PARP, transglutaminase, and Hsp27, in addition to TRPM‐2, are induced by androgen ablation in the rat ventral prostate and reach maximum levels between days 3 and 4 after castration. Using in situ hybridization we have established that these genes are expressed in the epithelial cells of the prostate that are known to undergo active cell death; this result suggests that their gene products may be required in the dying cells to ensure that the biochemical and morphological processes of apoptosis are completed appropriately.
Tunica Vaginalis Sperm Reservoir in a Monkey Model of Vas Deferens Obstruction
Authors: MONGA MANOJ , WANG RUN , ROBERTS JAMES A. , HELLSTROM WAYNE J. G.
Published: October 2023

ABSTRACT: Repeat microscopic epididymal sperm aspiration (MESA) is used to treat congenital absence of the vas deferens (CAVD). Use of alloplastic implants as reservoirs results in poor sperm motility and pregnancy rates. An autoplastic tunica vaginalis reservoir for epididymal sperm has been used in four patients, with one resultant pregnancy. We studied this technique in a monkey model. Eight reservoirs were created in four monkeys (Cercopithecus aethiops). The vas deferens was ligated close to the epididymis. A transverse incision was made in the caput epididymis, and sperm were aspirated for analysis. Cut margins of the epididymal duct were sutured open to the visceral layer of the tunica vaginalis. The defect in the parietal layer of the tunica vaginalis was repaired, and sterile Tyrode's solution was instilled in the potential space between the parietal and visceral layers. Initial epididymal sperm obtained at the creation of the sperm reservoir demonstrated adequate mean motility (60.5%, grade 1.5), morphology (82.8% normal), and viability by Eosin‐Y exclusion (69.9%). At 4 weeks, no reservoirs were palpable. Percutaneous aspiration (25‐gauge angiocatheter) yielded no fluid. Surgical exposure of the reservoirs demonstrated significant adhesions and scar formation between the parietal and visceral layers of the tunica vaginalis, obliterating the potential space. No sperm were detected in irrigant fluids at this time. In conclusion, adhesion and scar formation may prevent use of the tunica vaginalis reservoir as an alternative to repeat MESA in treatment of CAVD.
Effect of Follicular or Oviductal Fluids on Movement Characteristics of Bovine Sperm during Capacitation In Vitro
Authors: MCNUTT TAMARA L. , OLDS‐CLARKE PATRICIA , WAY AMY L. , SUAREZ SUSAN S. , KILLIAN GARY J.
Published: October 2023

ABSTRACT: Mammalian sperm exhibit characteristic motility changes associated with capacitation. Movement characteristics of bovine sperm incubated in noncapacitating (control, medium alone), capacitating (oviduct fluid, nonluteal, and luteal), or capacitating, acrosome reaction inducing (follicular fluid) conditions were investigated using a computer‐assisted automated semen analysis system. Sperm were incubated up to 4 hours in a modified Tyrode's medium (control), 20 and 60% nonluteal (NL) or luteal (L) oviduct fluid (ODF), or 20 and 60% follicular fluid (FF). Relative to sperm incubated in control medium, motility of sperm treated with ODF or FF had increased linearity and vigorous motility. Sperm incubated in 60% ODF or FF showed a small decrease in mean trajectory/path straightness and velocity over time compared to 20% fluid treatments and control. Frequency distribution graphs were symmetric for 20% NL‐ and L‐ODF treated sperm. However, 20% FF and 60% ODF and FF treatments had distributions skewed to the left, indicating smaller values for lateral head displacement (ALH) and curvilinear velocity (VOL). Me dian values for ALH and VCL were determined for control‐treated sperm, and subtracted from individual sperm values for all treatments to estimate deviation from control, designated ALHc and VCLc. Three‐dimensional plots of ALHc, VCLc and corresponding frequency indicated shifts in peak patterns for fluid‐treated sperm compared to control sperm. Incubation in 20% ODF and FF resulted in peak shift for ALH and VCL values; yet, little change in peak position was observed in sperm incubated in 60% ODF and FF. Although mean values decreased for ALH and VCL during the 4‐hour incubation, three‐dimensional plots suggested an increase in the frequency of individual sperm with these parameters. This study provides additional information on bovine sperm motion during in vitro capacitation and indicates that the presence of ODF and FF influences sperm motion characteristics.
Leukocytic Infiltration into the Human Ejaculate and Its Association with Semen Quality, Oxidative Stress, and Sperm Function
Authors: AITKEN R. J. , WEST K. , BUCKINGHAM D.
Published: October 2023

Immunocytochemical techniques have been used to monitor the size and composition of the leukocyte population in unfractionated human semen samples and sperm populations generated by Percoll® gradient centrifugation. The characteristics of the leukocyte population have then been related to the quality of the semen profile, the production of reactive oxygen species, and the functional competence of the spermatozoa. A majority (97%) of the ejaculates examined contained leukocytes, and in 82.4% the major cell type was the granulocyte. Small numbers of T cells, B cells, and monocytes/macrophages could also be found in 62%, 43%, and 21% of samples, respectively, and patients were occasionally identified in whom one of these cell types became the predominant leukocyte species. Although a subpopulation of patients was identified in whom the infiltration of multiple leukocyte species was positively correlated with the concentrations of spermatozoa and precursor germ cells in semen, in general, the presence of leukocytes, to the point of leukocytospermia, did not significantly influence any component of the semen profile. Similarly, the fertilizing potential of the washed spermatozoa, as assessed by in vitro tests of the acrosome reaction and sperm—oocyte fusion, was not correlated with the concentration of seminal leukocytes. In contrast, the carryover of leukocytes into the washed sperm preparations profoundly influenced the fertilizing potential of the spermatozoa via mechanisms that were associated with the production of reactive oxygen species. These results have implications for the diagnostic significance of leukocyte contamination in the context of male infertility and assisted conception.
Development of Computer‐Directed Methods for the Identification of Hyperactivated Motion Using Motion Patterns Developed by Rabbit Sperm During Incubation Under Capacitation Conditions
Authors: YOUNG RONALD J. , BODT BARRY A.
Published: October 2023

Rabbit spermatozoa developed motions that mimicked hyperactivated motility during incubation for 16–20 hours under capacitation conditions and in several other commonly used media. Sperm from some rabbits failed to acquire this type of motility, and sperm from others failed to survive the long incubation time. Four motility patterns developed during incubation for 16–20 hours. Motility parameters measured by the CellSoft and CellTrak motion analysis systems were similar except for the average amplitude of lateral head displacement. Multivariate discriminant analysis with complementary regression analysis, and an unrelated tree structured classification method (CART™), were used to derive rules, based on motility parameters, for the objective classification of sperm into the two motility classes: 1) nonhyperactivated motility and 2) hyperactivated motility or motility that mimicked hyperactivated motility. The motility parameter wobble (WOB) was superior to the commonly used parameter, linearity, as a classifier of motility types. It classified sperm into the two motility groups with 96.6% efficiency and, together with curvilinear velocity (VCL), attained classification efficiencies of 98%. The classification model produced by CART was preferred over the one obtained by discriminant analysis. The rule for motility classification was dependent on the motion analysis system used to measure the motion parameters. The rule for the CellSoft system, WOB ≤0.78 and VCL ≥51 μm/second, classified sperm with an efficiency of 98%, whereas the rule for the CellTrak system, WOB ≤0.69 and VCL ≥55 μm/second, achieved a classification efficiency of 97%. These rules should facilitate the study of sperm hyperactivation and its role in sperm function.
A New Method to Generate Canine Seminal Emission and Its Application to Men: Direct Electrical Stimulation of the Vas Deferens
Authors: KIHARA KAZUNORI , SATO KENJI , ANDO MASAO , USHIYAMA TAKEHISA , AZUMA HIROSHI , OSHIMA HIROYUKI
Published: October 2023

ABSTRACT: Seminal emission from the ejaculatory duct (SEED) by direct electrical stimulation of the vas deferens was investigated in the dog, and the technique was applied to men. The stimulus parameters used were 2 msec, 10 Hz, and 8 V for dogs or 15–20 V for humans. In vitro studies using tetrodotoxin demonstrated that the major portion of the muscle contraction under the above stimulation was neurogenic. The stimulation of the pars epididymica, the middle vas, or the ampulla of the vas caused SEED in all dogs having intact hypogastric nerves (HNs) and receiving transection of bilateral HNs 1, 6, and 12 months before electrical stimulation. The dye instilled into the canine cauda epididymis was transported to the ampulla and emitted into the posterior urethra by electrical stimulation of the vas regardless of the site stimulated. The electrical stimulation of eight vasa deferentia (pars epididymica) of five prostatic carcinoma patients generated emission from the severed proximal end of all vasa examined at orchidectomy. All of the stimulations of 13 middle vasa of seven patients with emission loss caused SEED. The above results indicate that direct electrical stimulation of the canine and human vas deferens causes SEED regardless of the site stimulated or the absence of HNs, which are the major pathway of the efferent signal for SEED.
Measurement of Immunoglobulin G Levels in Adult Rat Testicular Interstitial Fluid and Serum
Authors: HEDGER MARK P. , HETTIARACHCHI SHYAMANI
Published: October 2023

ABSTRACT: Total immunoglobulin G (IgG) in rat testicular interstitial fluid and serum was measured by two‐site enzyme‐linked immunosorbent assay, which displayed minimal cross‐reactivity with IgA or IgM. Normal adult testicular fluid IgG concentrations (2.67 ± 0.98 mg/ml) were found to be 65% of the levels found in serum. Disruption of seminiferous tubule function by experimental cryptorchidism had no effect on either testicular or serum IgG concentrations. Castration also had no effect on serum IgG concentrations. The effect of the Leydig cell cytotoxin, ethane dimethane sulfonate, on IgG concentrations was obscured by the observation that dimethyl sulfoxide (the carrier solvent) itself effectively eliminated the IgG concentration gradient across the testicular microvasculature. In normal and cryptorchid rats, serum IgG and thymus weights showed no correlation with serum inhibin concentrations measured by radioimmunoassay, although thymus weights were significantly increased in castrate rats. The data confirm that the permeability of the rat testis to circulating IgG is relatively high compared with other tissues and suggest that the testicular transendothelial transfer of IgG is unaffected by changes in testicular activity or hormone secretion. The high intratesticular concentration of IgG and its apparent lack of local regulation provide further evidence that the phenomenon of immune privilege in this tissue cannot be attributed simply to restriction of immune effectors from the testicular environment. The data also indicate that serum IgG levels in the adult male rat are not influenced in the short‐term by changes in peripheral testicular androgen levels. The direct effect of dimethyl sulfoxide on testicular endothelial permeability requires further investigation, as this solvent is used as a carrier for nonaqueous reagents in many studies of testicular function in vivo.
Heterogeneity of Gonadotropins and Levels of Uncombined Luteinizing Hormone Subunits in Pituitaries of Cryptorchid Rams
Authors: KEEL B. A. , ZALESKY D. D. , SOHAILI I. , SCHANBACHER B. D. , GROTJAN H. E.
Published: October 2023

ABSTRACT: Pituitaries were collected from intact rams and rams that had been rendered bilaterally cryptorchid by surgery to examine the effects of cryptorchidism on gonadotropin heterogeneity, levels of uncombined luteinizing hormone (LH) subunits, and the apparent molecular sizes of LH and follicle‐stimulating hormone (FSH). Cryptorchid rams had higher pituitary contents of LH and FSH as well as reduced testicular weights. The levels of uncombined LH subunits, their apparent molecular weights, and the apparent molecular weights of intrapituitary LH were similar in control and cryptorchid rams. However, the apparent molecular weight of intrapituitary FSH was slightly larger in cryptorchid rams. Cryptorchidism altered the pattern of gonadotropin heterogeneity by shifting the distribution of LH isoforms towards basic components and shifting the distribution of FSH isoforms towards acidic components. Thus, it appears that the altered gonadal feedback mechanisms resulting from cryptorchidism modify the pattern of both LH and FSH heterogeneity by shifting the distribution of isoforms in opposite directions.
Comparative Studies on Rabbit Corpus Cavernosal Contraction and Relaxation. An In Vitro Study
Authors: LEVIN ROBERT M. , HYPOLITE JOSEPH , BRODERICK GREGORY A.
Published: October 2023

ABSTRACT: Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators including nitric oxide. The specific aim of the current study was to determine the relative contribution of nitric oxide, adrenergic, purinergic, and cholinergic stimulation in the relaxant response to field stimulation. The results demonstrate that virtually all of the inhibitory effects of field‐stimulated relaxation could be explained by the release of nitric oxide. l‐NAME (l‐NG‐nitro arginine methyl ester, a competitive inhibitor of NO synthase) reduced field‐stimulated relaxation by over 95% at all frequencies. Neither atropine nor propranolol (or the combination of the two) had any significant effect on field‐stimulated relaxation. l‐NAME blocked both field‐stimulated relaxation and bethanechol‐stimulated relaxation. However, methylene blue (a guanyl cyclase inhibitor) was significantly more potent at blocking bethanechol‐stimulated relaxation than field‐stimulated relaxation. Neither l‐NAME nor methylene blue had any effect on nitroprusside (a direct liberator of NO) nor ATP‐stimulated relaxation. Isoproterenol had only a minor inhibitory effect on phenylephrine‐contracted tissue. These data suggest that 1) Methylene blue, which inhibits guanyl cyclase, is a relatively poor inhibitor of field‐stimulated relaxation. 2) l‐NAME is a potent inhibitor of NO synthesis and can in a dose‐dependent fashion inhibit over 95% of field‐stimulated relaxation. 3) Equipotent relaxation of corporal smooth muscle can be effected through pharmacologic stimulation with ATP (2 mM), nitroprusside (200 μM), and field stimulation (32 Hz). 4) If purinergic neurotransmission participates in physiologic erection, it does so by a mechanism independent of the l‐Arginine‐NO cGMP pathway.
Entactin Ultrastructural Immunolocalization in the Basal Laminae of Mouse Seminiferous Tubules and with Only Subtle Changes Following Hypophysectomy
Authors: LIAN GANG , ENDERS GEORGE C.
Published: October 2023

ABSTRACT: While entactin has been recently reported in the mouse seminiferous tubule lamina propria at the light microscope level, the purpose of this paper was twofold: 1) to determine the ultrastructural localization of entactin with the two basal laminae that form the lamina propria of the mouse, and 2) to determine if immunoreactive entactin changes following hypophysectomy. The localization of entactin was demonstrated by three different means: 1) immunofluorescent localization in semi‐thin cryosections of the testis, 2) immunoperoxidase staining in a preparation of isolated lamina propria, and 3) immuno‐gold staining in ultra‐thin sections of testis. These techniques all demonstrated that immunoreactive entactin is present in both the inner and outer basal laminae of the mouse seminiferous tubules and is co‐localized with laminin. These results are consistent with previous work that demonstrated entactin is synthesized and secreted by both Sertoli and peritubular myoid cells. Because both Sertoli cells and peritubular myoid cells are androgen‐responsive cells, we wanted to determine if hypophysectomy alters the testicular distribution of entactin. Changes in immunoreactive entactin and laminin in the basal laminae were observed in semi‐thin cryosections of the testes from hypophysectomized mice up to 6 weeks after surgery. The results demonstrated that during this time period, while most of the spermatogenic cells degenerated, the intensity of immunoreactive entactin and laminin remained nearly unchanged, as the seminiferous tubule basal laminae took on an increasingly wavy apparence. This suggests that the relative concentration of entactin and laminin in the basal lamina is stable, and not dependant on the presence of normal spermatogenesis and pituitary hormones.
Mitigating the curse of complexity: The role of focus and the implications for costs of care
Authors: Thirumalai Sriram , Devaraj Sarv
Published: October 2023

There has been a resurgence of interest in the role of operational focus in the healthcare operations literature in the backdrop of increasing demand for efficient and effective care. However, the evidence on the benefits of focus in healthcare is mixed. Our study proposes that a key piece of this puzzle that is been largely missing is an explicit consideration of the complexity of patient care needs. Specifically, our study serves to answer the questions: How does the complexity of care requirements affect care delivery operations? How does focus across the hierarchical levels of care affect care delivery outcomes across complexity regimes? The empirical analysis in the study is based on a large generalizable dataset of 246,663 patient discharges across 26 categories at 154 hospitals. We develop a multi‐factor measure of complexity of care requirements. The study results point to the deleterious impact of complexity on the costs of care. Next, our findings highlight the differential impact of focus across hierarchical levels (task‐level focus, category‐level focus, and selective focus in related areas) on the costs of care. Third, our study findings highlight the role of focus in mitigating the effects of complexity on costs in a healthcare setting. We discuss the implications of the study findings for theory and practice, and the directions for future research.
Femoral cartilage ultrasound echo‐intensity is a valid measure of cartilage composition
Authors: Harkey Matthew S. , Michel Nicholas , Grozier Corey , Slade Jill M. , Collins Katherine , Pietrosimone Brian , Lalush David , Lisee Caroline , Hacihaliloglu Ilker , Fajardo Ryan
Published: October 2023

This study aimed to create a conversion equation that accurately predicts cartilage magnetic resonance imaging (MRI) T2 relaxation times using ultrasound echo‐intensity and common participant demographics. We recruited 15 participants with a primary anterior cruciate ligament reconstruction between the ages of 18 and 35 years at 1–5 years after surgery. A single investigator completed a transverse suprapatellar scan with the ACLR limb in max knee flexion to image the femoral trochlea cartilage. A single reader manually segmented the femoral cartilage cross‐sectional area to assess the echo‐intensity (i.e., mean gray‐scale pixel value). At a separate visit, a T2 mapping sequence with the MRI beam set to an oblique angle was used to image the femoral trochlea cartilage. A single reader manually segmented the cartilage cross‐sectional area on a single MRI slice to assess the T2 relaxation time. A stepwise, multiple linear regression was used to predict T2 relaxation time from cartilage echo‐intensity and common demographic variables. We created a conversion equation using the regression betas and then used an ICC and Bland–Altman plot to assess agreement between the estimated and true T2 relaxation time. Cartilage ultrasound echo‐intensity and age significantly predicted T2 relaxation time (F = 7.33, p = 0.008, R2 = 0.55). When using the new conversion equation to estimate T2 relaxation time from cartilage echo‐intensity and age, there was strong agreement between the estimated and true T2 relaxation time (ICC2,k = 0.84). This study provides promising preliminary data that cartilage echo‐intensity combined with age can be used as a clinically accessible tool for evaluating cartilage composition.
Epicardial adipose tissue, metabolic disorders, and cardiovascular diseases: recent advances classified by research methodologies
Authors: Song Yujie , Tan Yanzhen , Deng Meng , Shan Wenju , Zheng Wenying , Zhang Bing , Cui Jun , Feng Lele , Shi Lei , Zhang Miao , Liu Yingying , Sun Yang , Yi Wei
Published: October 2023

Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy and physiology of the EAT determines its great potential in locally influencing adjacent tissues such as the myocardium and coronary arteries. Classified by research methodologies, this study reviews the latest research progress on the role of EAT in cardiovascular diseases (CVDs), particularly in patients with metabolic disorders. Studies based on imaging techniques demonstrated that increased EAT amount in patients with metabolic disorders is associated with higher risk of CVDs and increased mortality. Then, in‐depth profiling studies indicate that remodeled EAT may serve as a local mediator of the deleterious effects of cardiometabolic conditions and plays a crucial role in CVDs. Further, in vitro coculture studies provided preliminary evidence that the paracrine effect of remodeled EAT on adjacent cardiomyocytes can promote the occurrence and progression of CVDs. Considering the important role of EAT in CVDs, targeting EAT might be a potential strategy to reduce cardiovascular risks. Several interventions have been proved effective in reducing EAT amount. Our review provides valuable insights of the relationship between EAT, metabolic disorders, and CVDs, as well as an overview of the methodological constructs of EAT‐related studies.
Huntington Study Group's Neuropsychology Working Group: Implementing Non‐Motor Diagnostic Criteria
Authors: Considine Ciaran M. , Rossetti M. Agustina , Del Bene Victor A. , Anderson Kendra , Anderson Sharlet A. , Celka Andrea S. , Edmondson Mary C. , Nelson‐Sheese Amelia L. , Piccolino Adam , Teixeira Antonio L. , Stout Julie C.
Published: October 2023

Background

The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD‐consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non‐motor diagnostic criteria for HD.

Objectives

To provide (1) a recommended clinical approach toward non‐motor diagnostic criteria in persons with HD and facilitation of accurate diagnosis; (2) recommended practices for medical treatment providers to screen and longitudinally monitor non‐motor signs of HD.

Methods

The Huntington Study Group re‐established the Neuropsychology Working Group, then recruited a multi‐disciplinary group of neuropsychologists, neurologists, and psychiatrists to conduct an unstructured literature review and discuss expert opinions on practice, to facilitate an informal consensus opinion to accomplish the objectives.

Results

The opinion and an example protocol for medical treatment providers to screen, monitor, and triage non‐motor signs and symptoms of Huntington's disease is provided.

Conclusions

Clinical diagnosis of non‐motor HD is empirically justified and clinically important. Screening and triage by non‐neuropsychologist clinicians can aid in detecting and monitoring non‐motor Huntington's disease manifestation. The Neuropsychology Working Group consensus advances good clinical practice, clinical research, and quality of life. A companion position paper presenting the details of our consensus opinion regarding evidence‐based guidelines for neuropsychological practice is forthcoming.