Male infertility has seen an increase in prevalence with cases of azoospermia estimated to affect 10%-15% of infertile men. Confirmation of azoospermia subsequently necessitates an early causal differentiation between obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Although less common when compared to NOA, OA can represent upward 20%-40% of cases of azoospermia. While there are a multitude of etiologies responsible for causing NOA and OA, correctly distinguishing between the two types of azoospermia has profound implications in managing the infertile male. This review represents an amalgamation of the current guidelines and literature which will supply the reproductive physician with a diagnostic armamentarium to properly distinguish between NOA and OA, therefore providing the best possible care to the infertile couple.
Humans ; Azoospermia/etiology* ; Male ; Diagnosis, Differential ; Infertility, Male/etiology*

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Dental implants have restored masticatory function to over 100 000 000 individuals, yet almost 1 000 000 implants fail each year due to peri-implantitis, a disease triggered by peri-implant microbial dysbiosis. Our ability to prevent and treat peri-implantitis is hampered by a paucity of knowledge of how these biomes are acquired and the factors that engender normobiosis. Therefore, we combined a 3-month interventional study of 15 systemically and periodontally healthy adults with whole genome sequencing, fine-scale enumeration and graph theoretics to interrogate colonization dynamics in the pristine peri-implant sulcus. We discovered that colonization trajectories of implants differ substantially from adjoining teeth in acquisition of new members and development of functional synergies. Source-tracking algorithms revealed that this niche is initially seeded by bacteria trapped within the coverscrew chamber during implant placement. These pioneer species stably colonize the microbiome and exert a sustained influence on the ecosystem by serving as anchors of influential hubs and by providing functions that enable cell replication and biofilm maturation. Unlike the periodontal microbiome, recruitment of new members to the peri-implant community occurs on nepotistic principles. Maturation is accompanied by a progressive increase in anaerobiosis, however, the predominant functionalities are oxygen-dependent over the 12-weeks. The peri-implant community is easily perturbed following crown placement, but demonstrates remarkable resilience; returning to pre-perturbation states within three weeks. This study highlights important differences in the development of the periodontal and peri-implant ecosystems, and signposts the importance of placing implants in periodontally healthy individuals or following the successful resolution of periodontal disease.
Humans ; Dental Implants/microbiology* ; Microbiota ; Male ; Adult ; Female ; Biofilms ; Middle Aged ; Peri-Implantitis/microbiology*

Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications. In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner. However, existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes, thereby hindering a comprehensive understanding of their interactions. Here, we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria, respectively. Using a key oral pathobiont, Fusobacterium nucleatum, as the primary test bed, we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes. Compared to conventional models, this system enhanced bacterial invasion, elevated intracellular bacterial loads, and elicited more robust host pro-inflammatory responses, including increased secretion of CXCL10, IL-6, and IL-8. In addition, the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens. Finally, we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont, Porphyromonas gingivalis. These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics, offering a physiologically relevant approach to advance oral and systemic health research.
Coculture Techniques/methods* ; Humans ; Fusobacterium nucleatum/physiology* ; Gingiva/microbiology* ; Keratinocytes/microbiology* ; Host Microbial Interactions ; Mouth/microbiology* ; Host-Pathogen Interactions ; Epithelial Cells/microbiology* ; Cells, Cultured ; Porphyromonas gingivalis

Gastric remnant volvulus following Roux-en-Y gastric bypass (RYGB) surgery is rare, with only two previously reported cases. Herein, we present the first case of gastric remnant volvulus following gastric sleeve conversion to RYGB in a 32-year-old female. Management for gastric remnant volvulus has not been clearly described in the literature due to the rarity of cases;however, previously documented cases of gastric remnant volvulus following RYGB were managed with gastropexy or resection of the gastric remnant. Due to anatomical limitations, gastropexy was not an option for our patient, and the remnant stomach was resected.Although management options are still evolving, surgical intervention is likely indicated for gastric remnant volvulus that develops following RYGB. To improve patient outcomes and establish more comprehensive guidelines for this uncommon condition, further studies on the management of post-RYGB gastric remnant volvulus are warranted since gastric sleeve conversion to RYGB is becoming more prominent.

Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is highly prevalent among patients with neurologic disorders. Some studies have demonstrated that implantable neuromodulation can improve symptoms of NLUTD. We seek to describe our experience with sacral and pudendal neuromodulation in patients with NLUTD. Methods: A retrospective chart review of patients with “neurogenic bladder” ICD-9/10 (International Classification of Diseases, Ninth Revision/10th Revision) code was performed at a single institution. This included patients from 2008 to 2020 who underwent stage 1 neuromodulation trial. Demographic and clinical information was collected, including neurologic diagnosis, the character of patients’ voiding symptoms, the presence or absence of fecal incontinence, the need for intermittent catheterization, and whether patients had sufficient (>50%) improvement in their symptoms to undergo stage 2 implantable pulse generator (IPG) placement. Results: We identified 82 patients with neurologic diagnoses who underwent stage 1 neuromodulation. The most common diagnoses were diabetic cystopathy (17.07%), spinal surgery (17.07%), and spinal cord injury (12.20%). The most commonly reported symptoms were urinary urgency, and urge urinary incontinence. Overall, 59 patients (71.95%) advanced to stage 2 IPG placement including 72% of patients with sacral leads and 76% with pudendal leads. Conclusions Neuromodulation is feasible and effective in the treatment of NLUTD. Further investigation into its utilization is warranted.

Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is highly prevalent among patients with neurologic disorders. Some studies have demonstrated that implantable neuromodulation can improve symptoms of NLUTD. We seek to describe our experience with sacral and pudendal neuromodulation in patients with NLUTD. Methods: A retrospective chart review of patients with “neurogenic bladder” ICD-9/10 (International Classification of Diseases, Ninth Revision/10th Revision) code was performed at a single institution. This included patients from 2008 to 2020 who underwent stage 1 neuromodulation trial. Demographic and clinical information was collected, including neurologic diagnosis, the character of patients’ voiding symptoms, the presence or absence of fecal incontinence, the need for intermittent catheterization, and whether patients had sufficient (>50%) improvement in their symptoms to undergo stage 2 implantable pulse generator (IPG) placement. Results: We identified 82 patients with neurologic diagnoses who underwent stage 1 neuromodulation. The most common diagnoses were diabetic cystopathy (17.07%), spinal surgery (17.07%), and spinal cord injury (12.20%). The most commonly reported symptoms were urinary urgency, and urge urinary incontinence. Overall, 59 patients (71.95%) advanced to stage 2 IPG placement including 72% of patients with sacral leads and 76% with pudendal leads. Conclusions Neuromodulation is feasible and effective in the treatment of NLUTD. Further investigation into its utilization is warranted.

Gastric remnant volvulus following Roux-en-Y gastric bypass (RYGB) surgery is rare, with only two previously reported cases. Herein, we present the first case of gastric remnant volvulus following gastric sleeve conversion to RYGB in a 32-year-old female. Management for gastric remnant volvulus has not been clearly described in the literature due to the rarity of cases;however, previously documented cases of gastric remnant volvulus following RYGB were managed with gastropexy or resection of the gastric remnant. Due to anatomical limitations, gastropexy was not an option for our patient, and the remnant stomach was resected.Although management options are still evolving, surgical intervention is likely indicated for gastric remnant volvulus that develops following RYGB. To improve patient outcomes and establish more comprehensive guidelines for this uncommon condition, further studies on the management of post-RYGB gastric remnant volvulus are warranted since gastric sleeve conversion to RYGB is becoming more prominent.

Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is highly prevalent among patients with neurologic disorders. Some studies have demonstrated that implantable neuromodulation can improve symptoms of NLUTD. We seek to describe our experience with sacral and pudendal neuromodulation in patients with NLUTD. Methods: A retrospective chart review of patients with “neurogenic bladder” ICD-9/10 (International Classification of Diseases, Ninth Revision/10th Revision) code was performed at a single institution. This included patients from 2008 to 2020 who underwent stage 1 neuromodulation trial. Demographic and clinical information was collected, including neurologic diagnosis, the character of patients’ voiding symptoms, the presence or absence of fecal incontinence, the need for intermittent catheterization, and whether patients had sufficient (>50%) improvement in their symptoms to undergo stage 2 implantable pulse generator (IPG) placement. Results: We identified 82 patients with neurologic diagnoses who underwent stage 1 neuromodulation. The most common diagnoses were diabetic cystopathy (17.07%), spinal surgery (17.07%), and spinal cord injury (12.20%). The most commonly reported symptoms were urinary urgency, and urge urinary incontinence. Overall, 59 patients (71.95%) advanced to stage 2 IPG placement including 72% of patients with sacral leads and 76% with pudendal leads. Conclusions Neuromodulation is feasible and effective in the treatment of NLUTD. Further investigation into its utilization is warranted.

Gastric remnant volvulus following Roux-en-Y gastric bypass (RYGB) surgery is rare, with only two previously reported cases. Herein, we present the first case of gastric remnant volvulus following gastric sleeve conversion to RYGB in a 32-year-old female. Management for gastric remnant volvulus has not been clearly described in the literature due to the rarity of cases;however, previously documented cases of gastric remnant volvulus following RYGB were managed with gastropexy or resection of the gastric remnant. Due to anatomical limitations, gastropexy was not an option for our patient, and the remnant stomach was resected.Although management options are still evolving, surgical intervention is likely indicated for gastric remnant volvulus that develops following RYGB. To improve patient outcomes and establish more comprehensive guidelines for this uncommon condition, further studies on the management of post-RYGB gastric remnant volvulus are warranted since gastric sleeve conversion to RYGB is becoming more prominent.