bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Proliferation in the Dorsal and Lateral Lobes of the Rat Prostate During Postnatal Development
Authors: BANERJEE SUBHADRA , BANERJEE PARTHA P. , ZIRKIN BARRY R.
Published: October 2023

We have shown previously that cell proliferation occurs throughout the ducts of the rat ventral prostate during its postnatal development. Our objectives herein were to identify and quantify proliferating cells in the dorsal and lateral lobes, to quantify DNA synthetic activity in the distal and proximal segments of these lobes, and to compare the results obtained to the results of our previous studies of the ventral lobe. [3H]‐Thymidine, administered in vivo, was incorporated into both the distal and proximal segments of day 10–60 rat dorsal and lateral prostates. Quantitative analyses of autoradiographs revealed that the percentages of labeled cells in the distal and proximal segments of the dorsal and lateral lobes were not significantly different at days 45 and 60, and they were only slightly (though significantly) different at days 10 and 20. Biochemical analyses of [3H]‐thymidine incorporation similarly revealed no significant differences in the distal and proximal segments at days 45 and 60, and only small differences at days 10 and 20. The results of analyses of mitotic figures were consistent with the results of autoradiographic analyses, showing clearly that cell proliferation occurs throughout the rat dorsal and lateral prostates. These results show for the first time that cell proliferation occurs throughout the dorsal and lateral lobes, strikingly reminiscent of the proliferation pattern that we reported previously for the ventral lobe.
Characterization of K Currents in Cultured Human Corporal Smooth Muscle Cells
Authors: CHRIST G. J. , SPRAY D. C. , BRINK P. R.
Published: October 2023

In order to gain more mechanistic insight into the regulation of corporal smooth muscle tone, we conducted electrophysiological studies on homogeneous explant cell cultures of human corpus cavernosum smooth muscle. Patch clamp analyses in the whole cell mode revealed a mean resting potential of −43 = 4.9 m V (n = 12 cells). Large whole cell outward K currents were very prominent in these cells, and ranged from 0.5 to 1.5 nA. In some cells, a transient, voltage‐dependent A current accounted for a significant portion of the observed whole cell currents. Furthermore, stimulation with the calcium channel agonist BAY K 8644 or the K channel agonist pinacidil doubled the magnitude of the whole cell K current, as would be expected for maxi‐K (Kca) and metabolically gated K channels (KATP), respectively. Single channel recordings in the detached patch mode consistently revealed the presence of at least two K channels: 1) a Kca channel, with a conductance of = 190 pS; and 2) a putative delayed rectifier channel with a conductance of =50 pS. Furthermore, all channel types showed some degree of voltage and/or calcium sensitivity. In conclusion, the large magnitude of the whole cell K currents and the observed K channel heterogeneity indicate a potentially important role for these channels in modulating corporal smooth muscle tone.
Gastricsin‐Mediated Proteolytic Degradation of Human Seminal Fluid Proteins at pH Levels Found in the Human Vagina
Authors: SZECSI PAL B. , LILJA HANS
Published: October 2023

The proteolytic degradation of human seminal fluid proteins at acidic conditions has been investigated. Upon acidification to the pH level of the human vagina, autoproteolysis of most seminal fluid proteins occurred after 30 minute of incubation at 37°C. The degradation was unaffected by inhibitors of serine, thiol, or me‐tallo proteases, whereas pepstatin prevented any proteolysis. The proteins in seminal fluid depleted of the aspartic protease progastricsin did not degrade upon acidification. Readdition of the progastricsin restored the autoproteolytic ability of seminal fluid. Prostate‐specific antigen, prostatic acid phosphatase, and Zn‐α2‐glycoprotein are quickly degraded; albumin, transferrin, and lactoferrin are degraded more slowly. The low molecular weight fragments of semenogelin I and II and especially β‐microseminoprotein are somewhat resistant to proteolysis. These observations strongly suggest that the aspartic protease progastricsin is responsible for the autoproteolysis of seminal fluid proteins under acidic conditions. This suggests that the function of the enzyme is to degrade seminal fluid proteins deposited in the vagina; this in turn may decrease the antigenic load in the vagina and prevent immuno‐infertility.
Comparison of Motility and Flow Cytometric Assessments of Seminal Quality in Fresh, 24‐Hour Extended and Cryopreserved Human Spermatozoa
Authors: KRAMER R. Y. , GARNER D. L. , BRUNS E. S. , ERICSSON S. A. , PRINS G. S.
Published: October 2023

Functional differences among fresh 24‐hour extended and cryopreserved human spermatozoa were assessed using both computer‐assisted semen analysis (CASA) and flow cytometry. The objective was to determine if there were interrelationships among various qualitative parameters of the fresh and treated samples when assessed by these two automated methods. Fertile donor specimens (n = 15) were split and examined for sperm motility and curvilinear velocity using CASA within 1 hour postejaculation, after 24 hours in TEST—yolk buffer at 5° C and after cryopreservation in TEST—yolk—glycerol medium. Flow cytometric analyses were performed on 24‐hour extended and cryopreserved (CP) samples after fluorescent staining with rhodamine 123 to quantify mitochondrial function and carboxydimethyl fluorescein diacetate and propidium iodide to assess plasma membrane integrity. The percentages of spermatozoa with functional mitochondria and intact membranes along with the proportion of dead cells were identified and quantified by flow cytometry. Quadrant analyses of these data were used to determine the relative red and green fluorescent intensities. The initial sperm motility was correlated to the motility observed for the 24‐hour stored and the CP samples. The sperm velocity of both the initial and the 24‐hour extended samples was correlated to the velocity of CP samples. As for the comparison of the two automated methods for assessing seminal quality, the only sperm motion parameter that was correlated with a sperm population identified by flow cytometry (quadrant 4) was the curvilinear velocity of the sperm after 24 hours storage (r = 0.69) and after cryopreservation (r = 0.74). The present findings indicate that additional research is needed to determine if prefreeze analyses of donor sperm could be useful in predicting the post‐thaw integrity of CP samples and, thereby, be useful in screening potential semen donors.
Effects of Finasteride on the Rat Ventral Prostate
Authors: SHAO TSANG C. , KONG ANN , MARAFELIA PANAYOTA , CUNNINGHAM GLENN R.
Published: October 2023

ABSTRACT: The objectives of this study were to compare changes in the ventral prostate (VP) of young adult Sprague Dawley rats after 28 days of treatment with finasteride (F), a potent 5α‐reductase inhibitor, with those caused by castration (Cx). VP concentrations of DHT were reduced to 20.2% and 6.6% of controls (1,947 ± 207 pg/VP, mean ± SE) by F (5 or 20 mg/kg/day) and to 2.6% of controls by Cx. VP weights were reduced 49% and 54% by F and 88% by Cx. DNA/VP fell 25% and 15% with F treatment and 72% after Cx, whereas RNA and protein/VP were reduced 37–51% by F and 91–93% by Cx. The RNA/DNA and the protein/DNA ratios fell to 30–36% of controls after F treatment and to 70% of controls after Cx. The mRNA concentrations of the C3subunit of prostatein 28S ribosomal RNA fell after treatment with F (5 mg/kg/day) and after Cx, whereas the mRNA for TRPM‐2, an androgen‐suppressed protein associated with apoptosis, was increased only after castration. To examine further the effects of F on the rate of DNA synthesis, 7‐day regressed adult rats were treated for 3 days with testosterone propionate ± F, and incorporation of 3H‐thymidine in minced ventral prostates was determined. F inhibited 3H‐thymidine incorporation. We conclude that Cx causes a greater reduction in cell number/VP and a greater reduction in RNA and protein/cell than F and that the differences between F treatment and castration probably result from differences in prostatic concentrations of T. However, we cannot exclude the possibility that small differences in DHT contribute to these differences.
Testicular Steroidogenesis in the Aging Brown Norway Rat
Authors: ZIRKIN BARRY R. , SANTULLI ROSEMARY , STRANDBERG JOHN D. , WRIGHT WILLIAM W. , EWING LARRY L.
Published: October 2023

ABSTRACT: In seeking an animal model of age‐associated changes in the male reproductive tract, we examined the effects of age on the health and testicular steroidogenic activity of the Brown Norway rat, with comparisons made to the Sprague‐Dawley rat. When perfused in vitro under conditions of maximally stimulating luteinizing hormone significant age‐associated reductions were seen in testosterone production by testes of Sprague‐Dawley rats of 21–24 months of age and by testes of Brown Norway rats of 18–30 months of age. Decreases in the capacity of the testes to produce testosterone were reflected in age‐associated decreases in both serum testosterone and in testosterone concentration within the seminiferous tubule fluid. In contrast to the Sprague‐Dawley rat, changes in steroidogenic activity in the Brown Norway rat were not accompanied by the occurrence of pituitary adenomas, obesity, or testicular tumors. This, along with its longevity, make the Brown Norway strain a highly promising model for testicular aging.
Validation of an Improved In Vitro Bioassay to Measure LH in Diverse Species
Authors: DAHL KRISTINE D. , SARKISSIAN ARLEN
Published: October 2023

ABSTRACT: Cultured Leydig tumor cells (MA‐10) respond to luteinizing hormone by synthesizing and secreting progesterone (P). The specificity of the response to LH prompted us to develop this system for use as a simple and rapid in vitro bioassay for LH. The aims of this study were to (1) improve sensitivity and reproducibility, and (2) optimize the assay for use in diverse animal species. A minimum sensitivity was observed at 0.05 mlU/well of LH with 0.5 × 104 cells/well for 1.5 hours. At higher concentrations of LH, shorter incubation periods also significantly stimulated P production. Addition of human LH standard or serum samples resulted in a dose‐dependent increase in P production. Parallel dose‐dependent curves were observed with LH preparations from mammalian, avian, and amphibian species. In conclusion, these findings demonstrate that (1) the assay is rapid, sensitive, and reproducible; (2) serum LH levels analyzed using this assay and the mouse Leydig cell bioassay are comparable; (3) shorter incubation times suggest the implementation of this assay for rapid qualitative determination of LH surges; and (4) the assay can be used for the analysis of samples from diverse species, especially those lacking radioimmunoassays. Therefore, this assay system allows for the simple and rapid measurement of circulating bioactive LH levels in humans and diverse animal species, and should provide insight regarding the role of bioactive LH in physiological and pathological conditions.
Relationship of Semen Quality, Number of Sperm Inseminated, and Fertility in Rabbits
Authors: FARRELL PAUL B. , FOOTE ROBERT H. , SIMKIN MICHAEL E. , CLEGG ERIC D. , WALL ROBERT J.
Published: October 2023

ABSTRACT The relationship between the total number of sperm inseminated, semen quality, and fertility in rabbits was investigated, using fractionated or unfractionated semen and different diluting fluids. Semen was from Dutch‐belted males collected twice weekly with an artificial vagina. All does were superovulated except in Experiment 3. In Experiment 1, sperm were fractionated on discontinuous 4% and 10% bovine serum albumin columns. Sperm from each portion of the gradient, along with unfractionated controls, were diluted to give 0.25 × 106, 0.5 × 106, 1.0 × 106, and 2.0 × 106 total sperm per insemination. In Experiment 2, sperm were diluted with Dulbecco's phosphate‐buffered saline to provide 0.10 × 106, 0.50 × 106, and 1.0 × 106 total sperm per insemination, with minimal processing time. In Experiment 3, does were allowed to kindle after inseminating 0.1 × 106 or 1.0 × 106 sperm. In Experiment 4, sperm were diluted with TALP buffer: seminal plasma 1:1 to 0.025 × 106, 0.05 × 106, and 0.10 × 106 total sperm per insemination. Over 2,800 embryos or unfertilized oocytes were obtained either 24 or 48 hours after insemination to measure fertility. Sperm numbers required for normal fertility were 0.50 × 106 in Experiment 1 and only 0.05 × 106 in Experiment 4. This reduction presumably was due primarily to reduced processing time and diluent change. Litter size was normal with 0.1 × 106 sperm (Experiment 3). In Experiment 4, computer‐assisted sperm analysis (HTM 2030 system; Beverly, Massachusetts) was adapted to successfully screen out some of the “inter‐fering” granules in rabbit semen. The correlation between multiple characteristics of semen quality and fertility was 0.53 (P < 0.01). This correlation likely will be increased with refinements in instrumentation and reduced sperm numbers per insemination.
Alteration of mRNA Transcript Levels of Rat Testicular Cells Following Procarbazine Administration
Authors: POGACH L. M. , LI M. T. , QIAN L. , HUANG H. F. S.
Published: October 2023

ABSTRACT: The present study examined the effects of a single 400‐mg/kg dose of procarbazine upon various testicular mRNA transcript levels in adult Sprague‐Dawley rats. Northern blot hybridization was employed to measure the steady‐state mRNA levels of proteins specific for Sertoli cells (adrogen‐binding protein [ABP] and transferrin) and spermatids (protamine 1 and transitional protein 2). In addition, mRNA transcript levels were determined for germ cell‐specific hemiferrin and insulin‐like growth factor‐1 (IGF‐1), which in adult rats is present predominantly in primary spermatocytes. Further‐more, the chronology of the effects of procarbazine upon spermatogonial populations was examined in whole mounts of seminiferous tubules.

The effect of procarbazine upon spermatogenesis was first noted among mature A3, young A4, and B spermatogonia 48–72 hours after drug administration. These results indicate that A2 through intermediate spermatogonia were most susceptible to procarbazine. In addition, degeneration of spermatocytes and young spermatids was evident by 5 days.

Northern blot analysis of testicular poly (A)+ RNA revealed that the steady‐state levels of mRNA transcripts of the spermatid nuclear proteins (protamine 1, 700 bp; and transitional protein 2, 580 bp) remained relatively unchanged for 5 days after procarbazine administration but were significantly decreased by more than 70% by 7 days.

On the other hand, the steady‐state mRNA levels for the Sertoli cell proteins ABP (1.7 kb) and transferrin (2.7 kb) were decreased by 45% and 50% (P < 0.05), respectively, 2 days after procarbazine administration. Significant suppression of ABP mRNA levels persisted through day 5, with partial recovery noted on day 7.

The differential responses of mRNA transcript levels of proteins specific for Sertoli cells and for germ cells demonstrate that in addition to proliferating spermatogonia and differentiating spermatogenic cells, Sertoli cells are also susceptible to the effects of procarbazine.
Pregnancy with Microsurgical Vas Sperm Aspiration from a Patient with Neurologic Ejaculatory Dysfunction
Authors: BELKER ARNOLD M. , SHERINS RICHARD J. , BUSTILLO MARIA , CALVO LUCRECIA
Published: October 2023

ABSTRACT: Patients with neurologic ejaculatory dysfunction who wish to have a child commonly undergo electroejaculation, which, unfortunately, may fail to stimulate either antegrade or retrograde ejaculation of sperm. Even when sperm are obtained with electroejaculation, conception still may not be achieved. We describe the achievement of a pregnancy after the intrauterine insemination of sperm obtained from microsurgical aspiration of the vas deferens. The intrauterine insemination of electroejaculated sperm had failed to achieve a pregnancy on three previous occasions. The relative merits of vas sperm aspiration and electroejaculation as part of the assisted reproduction regimen for men who have neurologic ejaculatory dysfunction are discussed.
Pregnancy Obtained with Human Testicular Spermatozoa in an In Vitro Fertilization Program
Authors: Schoysman R. , Vanderzwalmen P. , Nijs M. , Segal L. , Segal‐Bertin G. , Geerts L. , Van Roosendaal E. , Schoysman‐Deboeck A.
Published: October 2023

ABSTRACT: The fertilizing capacity of human testicular spermatozoa and the positive outcome of an in vitro fertilization program open a wide range of opportunities for men suffering from obstructive and inoperable azoospermia. In six cases, subzonal sperm injection or intracytoplasmic sperm injection techniques were applied to inject testicular spermatozoa into human oocytes. The fertilization rate after testicular sperm injection reached 45%. Normal cleavage was observed and replacement of 10 embryos in 6 patients resulted in one chemical and one ongoing pregnancy.
Comparison of Different Methods of Treating Varicocele
Authors: LENK SEVERIN , FAHLENKAMP DIRK , GLIECH VOLKER , LINDEKE ANDREAS
Published: October 2023

ABSTRACT: Varicocele treatment was performed in 331 patients. One hundred fifteen patients were operated upon according to the technique of Bernardi (1947), 80 patients underwent occlusion of the testicular vein by detachable balloons, 47 patients were treated with percutaneous sclerotherapy, and 89 patients underwent laparoscopic varicocele treatment. The laparoscopic occlusion of the testicular vessels was done in two different ways: (1) coagulation of the testicular veins with electrocoagulating tweezers, and (2) occlusion of the suprainguinal testicular vessel with metal clips and transection of the vessels.

Laparoscopic Group 1 showed a clearly higher complication rate and recurrence rate in comparison with the other methods, whereas in Group 2 we observed the best results with only 4% complications and recurrences.

Because of its higher complication rate and recurrence rate, laparoscopic electrocoagulation of the testicular veins proved to be inadequate.
Clinical Outcome and Cost Comparison of Percutaneous Embolization and Surgical Ligation of Varicocele
Authors: DEWIRE DOUGLAS M. , Dr. ANTHONY J. THOMAS JR.  , ALK RANDALL M. , GEISINGER MICHAEL A. , LAMMERT GARY K.
Published: October 2023

ABSTRACT: We reviewed the records of 81 consecutive subfertile men with oligospermia and/or asthenospermia, treated for varicocele with either percutaneous embolization or surgical ligation between 1987 and 1991, and compared the outcomes and costs of the two procedures. All men had presented with infertility of at least 6 months duration, and in most cases female factors had been previously evaluated and treated. Patients were offered a choice of embolization or ligation of the internal spermatic vein. Forty‐five men (56%) underwent ligation, and 36 men (44%) opted for embolization. The mean age, serum follicle‐stimulating hormone, pretreatment sperm density, motility, and concentration of motile sperm were similar for the two groups. Seminal quality improved in 65% of all patients after varicocele ablation (46 of 71). Improvements were seen in postoperative sperm density (P < 0.01), motility (P < 0.002), and concentration of motile sperm (P < 0.001). Thirty‐nine percent of the assessable patients established pregnancies during the study interval (26 of 66). The two treatment groups did not differ significantly with regard to the likelihood of postoperative improvement in sperm density (P = 0.64), motility (P = 0.33), concentration of motile sperm (P = 0.11), or pregnancy rate (P = 0.83). Percutaneous embolization and surgical ligation of varicocele are equally effective in improving male infertility and cost about the same. Embolization offers the potential advantage of shorter recovery to full activity as compared to surgical ligation. Where experienced interventional radiologists are available, percutaneous embolization should be offered as an alternative to open ligation.
Our Experience with Pharmacological Erection Treatment of Erectile Dysfunction
Authors: HATTAT HALIM , OZKARA HAMDI , AKKUS EMRE , ALICI BÜLENT
Published: October 2023

ABSTRACT: Administration of vasoactive drugs intracavernously is a well‐known easily used and inexpensive alternative in treatment of a certain group of patients with erectile dysfunction. There are a few drugs used for this purpose, but we prefer papaverine as the first choice because it is easily available and inexpensive in our country. We used alprostadil only in nonresponders to papaverine or if there was any complication with papaverine. We present a series of 69 patients, 24 with psychogenic(34.8%), 27 with organic(39.1 %), and 18(26.1) with mixed etiology of erectile dysfunction, treated with intracavernous self‐injection therapy. Mean follow‐up of the patients was 13.6 months (7–30 months). In this study, 3,430 papaverine and 780 alprostadil injections were performed in 56 and 13 patients, respectively. In 75% of the papaverine injections and in 83% of the alprostadil injections, erections were achieved sufficient for sexual intercourse. During the follow‐up, there were not any abnormal alterations in liver function tests. The main complaint of the patients who used papaverine was a burning sensation (98%) during administration of the drug, which did not last more than 1 minute. Of 13 patients in the alprostadil group, 56.9% of the patients complained mainly of discomfort during erection.

We concluded that intracavernous therapy is a good and inexpensive option in the management of erectile dysfunction in carefully selected patients.
Caverject, a New Licensed Prostaglandin Preparation for Use in Erectile Dysfunction
Authors: COKER CHARLES , BETTOCCHI CARLO , PRYOR JOHN
Published: October 2023

ABSTRACT: Prostaglandin E, (PGE1) is the drug of choice for intracavernous injection because of its efficacy and low incidence of serious side effects. Alprostadil sterile solution (PGE1) is licensed for cardiac use and is not available in a satisfactory formulation for erectile dysfunction. Caveiject is a new freeze‐dried formulation, and this paper describes some of the studies that have led to it being licensed in the United Kingdom.

In the first phase, 14 men with erectile dysfunction of varying etiology and known responders to at least 10 n̈g of PGE1 were recruited into a multicenter, double‐blind crossover of Alprostadil sterile solution (Prostin VR Pediatric, Upjohn) and Alprostadil sterile powder (Caverject). Subjects were randomly allocated to receive a single fixed intracavemosal dose of either 0 (placebo), 2.5, 5, 10, and 20 μg of both formulations. Each subject received a total of two intracavemosal injections, each separated by a washout period of at least 7 days. The response was measured by Rigiscan and there was no difference in the response to the two formulations.

In the second phase, 30 patients were recruited from the outpatient clinic for a home self‐injection program with Caverject. The aim of this arm of the study was to determine the response to and the acceptability of home self‐injection with the new formulation. All patients underwent a full clinical evaluation and laboratory investigations. Patients were instructed on injection technique and assessed at monthly intervals by means of diaries.

Nine patients withdrew from the study and the reasons were a failure of response (two), the inability to learn the technique (one), dissatisfaction with treatment (five), and progression of multiple sclerosis (one).

The remaining 21 patients were self‐injecting the drug at home and were still satisfied after 6 months, 76% of patients achieving full erection more than 75% of the time. The median frequency of injection was 5 (1–12) times a month. Mild pain after injection was reported in 8 patients (38%); no patient complained of severe pain or discontinued use because of discomfort. One patient sustained a prolonged erection of 340 minutes but this subsided after brief exercise. Subsequent dose reduction prevented recurrence.

The efficacy and low incidence of serious side effects makes this preparation the ideal choice for self‐injection, and it is the only preparation licensed for this purpose.
Impact of inhalation exposure to cigarette smoke on the pathogenesis of pulmonary hypertension primed by monocrotaline in rats
Authors: Park Jung‐Min , Seo Yoon‐Seok , Kim Sung‐Hwan , Kim Hyeon‐Young , Kim Min‐Seok , Lee Moo‐Yeol
Published: October 2023

Extensive, long‐term exposure to cigarette smoke (CS) was recently suggested to be a risk factor for pulmonary hypertension, although further validation is required. The vascular effects of CS share similarities with the etiology of pulmonary hypertension, including vascular inflammation and remodeling. Thus, we examined the influence of CS exposure on the pathogenesis of monocrotaline (MCT)‐induced pulmonary hypertension, hypothesizing that smoking might accelerate the development of primed pulmonary hypertension. CS was generated from 3R4F reference cigarettes, and rats were exposed to CS by inhalation at total particulate matter concentrations of 100–300 μg/L for 4 h/day, 7 days/week for 4 weeks. Following 1 week of initial exposure, rats received 60 mg/kg MCT and were sacrificed and analyzed after an additional 3 weeks of exposure. MCT induced hypertrophy in pulmonary arterioles and increased the Fulton index, a measure of right ventricular hypertrophy. Additional CS exposure exacerbated arteriolar hypertrophy but did not further elevate the Fulton index. No significant alterations were observed in levels of endothelin‐1 and vascular endothelial growth factor, or in hematological and serum biochemical parameters. Short‐term inhalation exposure to CS exacerbated arteriolar hypertrophy in the lung, although this effect did not directly aggravate the overworked heart under the current experimental conditions.
MiniMounter: A low‐cost miniaturized microscopy development toolkit for image quality control and enhancement
Authors: Zhu Xinyi , Gu Liangtao , Li Rui , Chen Liang , Chen Jingying , Zhou Ning , Ren Wuwei
Published: October 2023

Head‐mounted miniaturized fluorescence microscopy (Miniscope) has emerged as a significant tool in neuroscience, particularly for behavioral studies in awake rodents. However, the challenges of image quality control and standardization persist for both Miniscope users and developers. In this study, we propose a cost‐effective and comprehensive toolkit named MiniMounter. This toolkit comprises a hardware platform that offers customized grippers and four‐degree‐of‐freedom adjustment for Miniscope, along with software that integrates displacement control, image quality evaluation, and enhancement of 3D visualization. Our toolkit makes it feasible to accurately characterize Miniscope. Furthermore, MiniMounter enables auto‐focusing and 3D imaging for Miniscope prototypes that possess solely a 2D imaging function, as demonstrated in phantom and animal experiments. Overall, the implementation of MiniMounter effectively enhances image quality, reduces the time required for experimental operations and image evaluation, and consequently accelerates the development and research cycle for both users and developers within the Miniscope community.
Surface immobilized α‐1 acid glycoprotein and collagen VI modulate mouse macrophage polarization and reduce the foreign body capsule
Authors: Chen Alex C. , Ciridon Winston , Creason Sharon , Ratner Buddy D.
Published: October 2023

Macrophages are widely recognized in modulating the foreign body response, and the manner in which they do so largely depends on their activation state, often referred to as their polarization. This preliminary study demonstrates that surface immobilized α‐1 acid glycoprotein (AGP), as well as collagen VI (Col6) in conjunction with AGP, can direct macrophages towards the M2 polarization state in vitro and modify the foreign body response in vivo. AGP and Col6 are immobilized onto poly(2‐hydroxyethyl methacrylate) (pHEMA) surfaces using carbonyl diimidazole chemistry. Mouse bone marrow derived macrophages are cultured on modified surfaces with or without lipopolysaccharide stimulation. Surface modified pHEMA discs are implanted subcutaneously into mice to observe differences in the foreign body response. After stimulation with lipopolysaccharide, macrophages cultured on AGP or Col6 modified surfaces showed a reduction in TNF‐α expression compared to controls. Arg1 expression was also increased in macrophages cultured on modified surfaces. Explanted tissues showed that the foreign body capsule around implants with AGP or AGP and Col6 modification had reduced thickness, while also being more highly vascularized. These data demonstrate that α‐1 acid glycoprotein and collagen VI could potentially be used for the surface modification of medical devices to influence macrophage polarization leading to a reduced and modulated foreign body response.
Oxide degradation precedes additively manufactured Ti‐6Al‐4V selective dissolution: An unsupervised machine learning correlation of impedance and dissolution compared to Ti‐29Nb‐21Zr
Authors: Kurtz Michael A. , Alaniz Kazzandra , Kurtz Peter W. , Wessinger Audrey C. , Moreno‐Reyes Aldo , Gilbert Jeremy L.
Published: October 2023

Additively manufactured (AM) Ti‐6Al‐4V devices are implanted with increasing frequency. While registry data report short‐term success, a gap persists in our understanding of long‐term AM Ti‐6Al‐4V corrosion behavior. Retrieval studies document β phase selective dissolution on conventionally manufactured Ti‐6Al‐4V devices. Researchers reproduce this damage in vitro by combining negative potentials (cathodic activation) and inflammatory simulating solutions (H2O2‐phosphate buffered saline). In this study, we investigate the effects of these adverse electrochemical conditions on AM Ti‐6Al‐4V impedance and selective dissolution. We hypothesize that cathodic activation and H2O2 solution will degrade the oxide, promoting corrosion. First, we characterized AM Ti‐6Al‐4V samples before and after a 48 h −0.4 V hold in 0.1 M H2O2/phosphate buffered saline. Next, we acquired nearfield electrochemical impedance spectroscopy (EIS) data. Finally, we captured micrographs and EIS during dissolution. Throughout, we used AM Ti‐29Nb‐21Zr as a comparison. After 48 h, AM Ti‐6Al‐4V selectively dissolved. Ti‐29Nb‐21Zr visually corroded less. Structural changes at the AM Ti‐6Al‐4V oxide interface manifested as property changes to the impedance. After dissolution, the log‐adjusted constant phase element (CPE) parameter, Q, significantly increased from −4.75 to −3.84 (Scm−2(s)α) (p = .000). The CPE exponent, α, significantly decreased from .90 to .84 (p = .000). Next, we documented a systematic decrease in oxide polarization resistance before pit nucleation and growth. Last, using k‐means clustering, we established a structure–property relationship between impedance and the surface's dissolution state. These results suggest that AM Ti‐6Al‐4V may be susceptible to in vivo crevice corrosion within modular taper junctions.
Left ventricular reverse remodeling after transcatheter aortic valve replacement for predominant aortic stenosis and mixed aortic valve disease
Authors: Huang Liangyan , Lai Xiaoyue , Xu Lei , Zeng Ziling , Xia Hongmei
Published: October 2023

Background

Mixed aortic valve disease (MAVD) is a frequent concomitant valve disease with unique cardiac pathological changes compared to predominant aortic stenosis (PAS). The previous studies about the MAVD are contradictory. Therefore, a new perspective is needed to assess the value of TAVR for this cohort of patients.

Methods

From January 2018 to December 2021, 90 MAVD patients and 72 PAS patients who underwent TAVR in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The dynamic changes in left ventricular morphology and hemodynamics were compared by generalized estimating equations. Univariate or multivariate logistic regression analysis was used to screen for independent risk factors for the non‐occurrence of left ventricular reverse remodeling (non‐LVRR).

Results

After the matching procedure, 112 patients were included in the analysis (56 in each group). Baseline characteristics were similar between the two groups. LVRR occurred in both groups, but MAVD had greater left ventricular end‐diastolic volume index and left ventricular mass index, a higher incidence of mitral regurgitation (MR), and a more pronounced transformation of ventricular geometry patterns. Post‐operative MR (odd ratio [OR]: 10.05; 95% confidence interval [CI]: 2.08–48.57; p < .001) and coronary artery disease (OR: 2.82; 95% CI: 1.08–7.34; p = .034) were independent risk factors for non‐LVRR.

Conclusion

LVRR also occurs in patients with MAVD, post‐operative MR and coronary artery disease were independent risk factors for non‐LVRR.
Emunas Chachamim (faith in the sages): A prenatal genetic counseling needs assessment of Orthodox Jewish clergy in Los Angeles
Authors: Richeimer Natalie , Wilson Kaila , Petrasek Alexandra , Weiner Jason
Published: October 2023

The Jewish population's high risk for certain genetic conditions is well established. The Orthodox Jewish community, a denomination of the larger Jewish population, has distinct customs and cultural practices and a complex relationship with Western medicine and medical genetics. Clergy play a central role as stakeholders in the Orthodox Jewish community, and their input often informs key medical decisions for their congregants. Orthodox clergy have a unique structure for advising their community members, which is based on Jewish law. A qualitative research methods study was conducted to learn more about the needs of Orthodox Jewish clergy in the greater Los Angeles area with regard to prenatal genetic testing. The present study aims to understand the function of clergy, cultural implications in genetics care, and ways to improve cooperation between clergy and medical providers. 18 clergy members were recruited to join the study, with a 100% participation rate. Thematic analysis of individual interviews highlighted four major themes: the multitude of roles of clergy; pragmatic testing; a need for mutual respect; and interactions between medical providers and clergy. The existing community infrastructure may be used as the framework to provide a greater awareness of genetic care to this community. Future research should be conducted to explore how to improve interactions between genetic counselors and Orthodox Jewish clergy and the best practices for cultural competency.
Variations of the hepatic artery and bile duct in patients with pancreaticobiliary maljunction: Impact on postoperative outcomes
Authors: Takada Shunya , Uchida Hiroo , Hinoki Akinari , Shirota Chiyoe , Sumida Wataru , Tainaka Takahisa , Makita Satoshi , Takimoto Aitaro , Nakagawa Youichi , Maeda Takuya
Published: October 2023

Purpose

Preoperative comprehension of the anatomical variations of the hepatic artery and bile duct is essential for safe laparoscopic surgery for pancreaticobiliary maljunction (PBM). This study aimed to investigate the impact of anatomical variations of the hepatic artery and bile duct on surgical technique and postoperative complications.

Methods

We conducted a retrospective review of patients with PBM who underwent laparoscopic surgery at our institution between January 2014 and December 2022 to investigate anatomical variations in the hepatic artery and bile duct, surgical technique, and postoperative complications.

Results

We included 112 patients with PBM, with a median age of 4 years (interquartile range, 0–55). Overall, 29 of 112 patients had an aberrant right hepatic artery (ARHA) running ventral to the common hepatic duct (CHD), and they underwent hepaticojejunostomy on the ventral side of the ARHA. Additionally, eight of 112 patients had an aberrant posterior hepatic duct (APHD), which was joined to the CHD in all but one case. The presence of APHD was associated with postoperative bile leak occurrence.

Conclusion

Performing hepaticojejunostomy ventral to the ARHA is important to prevent complications. Furthermore, APHD may be a risk factor for postoperative bile leak and requires careful bile duct plasty.
Age and Gender‐Dependence of Single‐and Bi‐Exponential T1ρ MR Parameters in Knee Ligaments
Authors: Lise de Moura Hector , Kijowski Richard , Zhang Xiaoxia , Sharafi Azadeh , Zibetti Marcelo V. W. , Regatte Ravinder
Published: October 2023

Background

There is limited understanding of differences in the composition and structure of ligaments between healthy males and females, and individuals of different ages. Females present higher risk for ligament injuries than males and there are conflicting reports on its cause. This study looks into T1ρ parameters for an explanation as it relates to proteoglycan, collagen, and water content in these tissues.

Purpose

To investigate gender‐related and age‐related differences in T1ρ parameters in knee joint ligaments in healthy volunteers using a T1ρ‐prepared zero echo‐time (ZTE)‐based pointwise‐encoding time‐reduction with radial acquisition (T1ρ‐PETRA) sequence.

Study Type

Prospective.

Population

The study group consisted of 22 healthy subjects (11 females, ages: 41 ± 18 years, and 11 males, ages: 41 ± 14 years) with no known inflammation, trauma, or pain in the knee joint.

Field Strength/Sequence

A T1ρ‐prepared 3D‐PETRA sequence was used to acquire fat‐suppressed images with varying spin‐lock lengths (TSLs) of the knee joint at 3T.

Assessment

Monoexponential, biexponential, and stretched‐exponential 3D‐PETRA‐T1ρ parameters were measured in the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and patellar tendon (PT) by manually drawing ROIs over the entirety of the tissues.

Statistical Tests

Mann–Whitney U‐tests were used to compare 3D‐PETRA‐T1ρ parameters in the ACL, PCL, and PT between males and females. Spearman correlation coefficients were used to determine the association between age and T1ρ parameters. Statistical significance was defined as P < 0.05.

Results

Significant correlations with age were found the three ligaments with most of the measured T1ρ parameters (rs = 0.28–0.74) with the exception of the short fraction in the PCL (P = 0.18), and the short relaxation time in the ACL (P = 0.58) and in the PCL (P = 0.14).

Data Conclusion

3D‐PETRA‐T1ρ can detect age‐related differences in monoexponential, biexponential, and stretched‐exponential T1ρ parameters in three ligaments of healthy volunteers, which are thought to be related to changes in tissue composition and structure during the aging process.

Level of Evidence

2

Technical Efficacy

Stage 1
Re‐Creating Higher Education Pedagogy by Making Materiality and Spatiality Matter
Authors: Chappell Kerry , Witt Sharon , Wren Heather , Hampton Leonie , Woods Pam , Swinford Lizzie , Hampton Martin
Published: October 2023

This study marks a resting point within ongoing explorations of creativity, transdisciplinarity, materiality, and spatiality in Higher Education (HE) pedagogy. It interrogates how different materialities and spatialities shape learning to re‐create practices to better respond to societal challenges. This is situated within an imperative to move away from Western‐dominated approaches to pedagogy and research, where “Western” is characterized as onto‐epistemological rather than place‐based. The study draws on postqualitative enquiry into two creative, transdisciplinary HE courses, which entwined the arts, sciences, and entrepreneurship to facilitate responses to societal problems. Framed using posthumanizing creativity, the research aims to decenter the human and posit creativity as a dialogic, intra‐active process with the capacity to change education from within. A postqualitative approach works through three data diffractions. The first two involve glow moments used for collaging, cut through with theory. The third diffraction involves glow moments from which a short dance film was created. The study aims to stir readers/engagers to action their creativity as feeding forward into their own work in HE pedagogies, to consider how to move beyond the word, and the influences all of this can have on reimagining practices and changing structures.
Effect of Matrix Stiffness and Hepatocyte Growth Factor on Small Cell Lung Cancer Cells in Decellularized Extracellular Matrix‐Based Hydrogels
Authors: Han Yoobin , Ki Chang Seok
Published: October 2023

Small cell lung cancer (SCLC) is one of lethal cancers resulting in very low 5‐year‐survival rate. Although its clinical treatment largely relies on chemotherapy, SCLC cell physiology in three‐dimenstional (3D) matrix has been less explored. In this work, the tumor microenvironment is reconstructed with decellularized porcine pulmonary extracellular matrix (dECM) with hyaluronic acid. To modulate matrix stiffness, the methacrylate groups are introduced into both dECM and hyaluronic acid, followed by photocrosslinking with photoinitiator. The stiffness of the resulting dECM‐based hydrogel covers the stiffness of normal or cancerous tissue with varying dECM content. The proliferation and cancer stem cell marker expression of encapsulated SCLC cells are promoted in a compliant hydrogel matrix, which has a low shear modulus similar to that of the normal tissue. The hepatocyte growth factor (HGF) that induces SCLC cell invasion and chemoresistance markedly increases invasiveness and gene expression levels of CD44 and Sox2 in the hydrogel matrix. In addition, HGF treatment causes higher resistance against anticancer drugs (cisplatin and paclitaxel) in the 3D microenvironment. These findings indicate that malignant SCLC can be recapitulated in a pulmonary dECM‐based matrix.
Transparent and Soft Crack‐Resistant Bouligand Elastomers Inspired by Fish Scales
Authors: Shu Jingheng , Teng Qiancheng , Zhang Hao , Wu Jinrong , Liu Zhan
Published: October 2023

Nature with its abundant source offers numerous inspirations for structural and engineering designs. The oriented membranes stacked with bouligand structures in the fish scales show an outstanding combination of high strength and crack resistance. Although the applications of hard biomimetic composites are reported, the structures are rarely utilized in soft materials. Inspired by the scales of various fishes, electrospun membranes are used and stacked to fabricate bouligand elastomers, including orthogonal‐plywood, single‐bouligand, and double‐bouligand structures. The effects of different structures on the properties of elastomers are systematically investigated and possible mechanism is explained using finite element analysis (FEA). The stiffness and fatigue characteristics of these biomimetic elastomers with the above structures are improved compared with the original membranes, especially the elastomers with a single‐bouligand structure, which can undergo 5 000 cycles at a maximum strain of 35% without complete failure. The crack only propagates to half of the width of the elastomer with remaining strength of 50% of its original strength. Moreover, the mechanical performance can be adjusted by regulating the proportion of the components. The excellent crack‐resistant properties and transparency promote its various potential applications.
Valproic acid increased the efficacy of EGFR TKIs on EGFR/TP53 co‐mutated lung cancers and downregulated mutant‐p53 levels
Authors: Hu Mengdi , Cheng Hanyue , Yang Yijing , Xu Lu
Published: October 2023

The TP53 tumor suppressor is the most frequently mutated gene in human cancers. For p53‐targeted therapy, one of the strategies was targeting mutant p53 for degradation. In EGFR‐mutated lung cancer patients, concurrent TP53 mutation was associated with faster resistance to EGFR‐TKIs. In this study, we discovered that valproic acid (VPA), a widely prescribed antiseizure medication, had a synergic effect on sensitive as well as acquired resistant lung cancers with EGFR/TP53 co‐mutation in combination with EGFR‐TKIs. In both in vitro and in vivo models, VPA greatly improved the efficacy of EGFR‐TKIs, including forestalling the occurrence of acquired resistance and increasing the sensitivity to EGFR‐TKIs. Mechanistically, VPA dramatically promoted degradation of mutant p53 in both sensitive and acquired resistant cells while inhibited mutant TP53 mRNA transcription only in sensitive cells. Together, this study suggested that VPA combination treatment could have beneficial effects on EGFR‐mutant lung cancers with concurrent p53 mutation in both early and late stages, expanding the potential clinical applications for VPA.
COPA syndrome caused by a novel p.Arg227Cys COPA gene variant
Authors: Zheng Yue , Du Yue , Wu Yubin , Li Fuwei , Gu Weiyue , Zhao Chengguang
Published: October 2023

Background

COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway. To date, 59 cases of COPA have been reported worldwide.

Methods

In this case, Trio‐whole exome sequencing was employed in the proband and her parents to identify the underlying genetic cause. COPA variant were detected and the clinical presentation of the patient was described.

Results

Herein, we report a case of a 5‐year‐old girl with COPA syndrome who presented with symptoms of arthritis combined with Anti‐neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV), and progressive renal decline with minimal pulmonary involvement. Trio‐whole exome sequencing was performed which revealed a novel heterozygous likely pathogenic variation in the COPA gene (c.679C>T,p.Arg227Cys), which was maternally inherited. Her mother was a heterozygote, but she had no phenotypic manifestations. No other mutations associated with the clinical phenotype were identified.

Conclusion

The present identification and characterization of a novel mutation expands the genotypic spectra of the COPA syndrome and provide reference data to guide future clinical diagnosis and treatment of COPA syndrome.