Unknown Factors Research Articles

Importance of Circulating Leptin and Adiponectin in the Causal Pathways Between Obesity and the Development of Colorectal Cancer in Japanese Men.

The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively). We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men. BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0-27.4 kg/m2 (risk ratio 1.29; 95% confidence interval, 0.98-1.69) and ≥27.5 kg/m2 (risk ratio 1.28; 95% confidence interval, 0.98-1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin. Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.

Fixed-time adaptive control of quadrotor suspension system with unknown payload mass

This paper investigates the control challenges of quadrotor suspension systems with unknown payload masses. To address the unknown external disturbances, uncertainties in system models, and unknown payloads, fixed-time stable adaptive laws are developed to estimate and compensate for these unknown factors. Additionally, a novel control structure based on a nonlinear backstepping controller is proposed for the quadrotor suspension system, achieving stable control of the quadrotor and reducing the sway of the suspended payload. The fixed-time stability of the designed closed-loop system is analytically proven using Lyapunov functions, ensuring maximum stability time. Simulink simulations validate the proposed control approach, demonstrating accurate estimation of unknown masses and the effectiveness and superiority of the controller.

Recovery of hearing loss in atypical Meniere’s disease after treatment with orofacial and neck massage: A case report

BACKGROUND A 48-year-old female presented with sudden-onset right-sided aural fullness, low-frequency hearing loss, and tinnitus. Medical history included right-sided temporomandibular joint disorder (TMJD) with crepitation, and retro-orbital headaches. The patient was diagnosed with atypical Meniere’s disease (MD) and received intratympanic steroids, prednisone, betahistine, and began a low-sodium diet; however, the patient’s symptoms worsened. CASE SUMMARY The patient sought physical therapy for TMJD; testing revealed reduced motion and dysfunction with vertical opening, lateral excursion of the mandible to the right, and tenderness to palpation. Treatment included soft tissue mobilization of right facial structures and temporal fossa, intraoral massage of the right pterygoid musculature, and massage of right neck structures. After 4 weeks, the patient noticed subjective improvement in hearing and decreased headaches. After 11 weeks, an audiogram showed that the hearing loss had recovered. The patient has continued the daily at-home intraoral/neck massage therapy and maintained normal hearing over 4 years to date. The temporal relationship between physical therapy and recovery of hearing loss suggests muscular or inflammatory etiology as at least partially causative of this patient’s symptoms. The mechanism of healing may have been due to decreased inflammation, improved blood flow, restored function of cranial nerves, or some combination of these and other unknown factors. CONCLUSION This report suggests that orofacial physical and massage therapy may be an effective treatment for the cochlear symptoms associated with MD.

Dynamics of Natural Mortality Factors of Immature Diatraea saccharalis (Fabricius) (Lepidoptera: Crambidae) in Sugarcane Adjacent to Forest Fragments

ABSTRACTPest regulation may be favoured in crop fields adjacent to semi‐natural vegetation such as fragments of the Atlantic Forest in Southeastern Brazil. Therefore, the objective of this study was to analyse the dynamics of mortality factors for eggs and larvae of Diatraea saccharalis (Lepidoptera: Crambidae) in sugarcane adjacent to two types of forest fragments (Plateau and Gallery) at two distances from these fragments during two growing seasons. In each area (seven sugarcane plots), two 50 m long transects were established, parallel and spaced at 5 and 100 m from the field edge, and cohorts of the insect at each stage of development were monitored. The collected data were used to construct an ecological life table and determine the main mortality factors. Natural mortality factors that could not be characterised were grouped as unknown. In both seasons and stages of development observed, there was no difference in mortality between the two types of forest fragments (Plateau and Gallery) or between the two distances from the forest. For the egg stage, the mortality factors were classified as inviable due to infertility, predation, parasitism, desiccation and dislodgement. In both seasons, there was a significant difference in the natural mortality factors of D. saccharalis, with predation distinct from the others. Ants (Hymenoptera: Formicidae) and green lacewings (Neuroptera: Chrysopidae) were the most frequent predatory agents and occurred at both distances and types of forest fragments. For the larval stage, the mortality factors were classified as predation, parasitism, drowning and unknown, with the unknown group differing from the others. Unknown factors might have included predation, larval movement towards other plants and displacement caused by wind after hatching. Overall, predation is a key mortality component of D. saccharalis suppression. Therefore, agricultural practices focused on the conservation of natural enemies such as predators may provide more sustainable management.

Capturing resilience from phenotypic deviations: a case study using feed consumption and whole genome data in pigs

BackgroundIn recent years, interest has grown in quantifying resilience in livestock by examining deviations in target phenotypes. This method is based on the idea that variability in these phenotypes reflects an animal’s ability to adapt to external factors. By utilizing routinely collected time-series feed intake data in pigs, researchers can obtain a broad measure of resilience. This measure extends beyond specific conditions, capturing the impact of various unknown external factors that influence phenotype variations. Importantly, this method does not require additional phenotyping investments. Despite growing interest, the relationship between resilience indicators—calculated as deviations from longitudinally recorded target traits—and the mean of those traits remains largely unexplored. This gap raises the risk of inadvertently selecting for the mean rather than accurately capturing true resilience. Additionally, distinguishing between random phenotype fluctuations (white noise) and structural variations linked to resilience poses a challenge. With the aim of developing general resilience indicators applicable to commercial swine populations, we devised four resilience indicators utilizing daily feed consumption as the target trait. These include a canonical resilience indicator (BALnVar) and three novel ones (BAMaxArea, SPLnVar, and SPMaxArea), designed to minimize noise and ensure independence from daily feed consumption. We subsequently integrated these indicators with Whole Genome Sequencing using SLEMM algorithm, data from 1,250 animals to assess their efficacy in capturing resilience and their independence from the mean of daily feed consumption.ResultsOur findings revealed that conventional resilience indicators failed to differentiate from the mean of daily feed consumption, underscoring potential limitations in accurately capturing true resilience. Notably, significant associations involving conventional resilience indicators were identified on chromosome 1, which is commonly linked to body weight.ConclusionWe observed that deviations in feed consumption can effectively serve as indicators for selecting resilience in commercial pig farming, as confirmed by the identification of genes such as PKN1 and GYPC. However, the identification of other genes, such as RNF152, related to growth, suggests that common resilience quantification methods may be more closely related to the mean of daily feed consumption rather than capturing true resilience.

A systematic quantitative approach comprehensively defines domain-specific functional pathways linked to Schizosaccharomyces pombe heterochromatin regulation.

Heterochromatin plays a critical role in regulating gene expression and maintaining genome integrity. While structural and enzymatic components have been linked to heterochromatin establishment, a comprehensive view of the underlying pathways at diverse heterochromatin domains remains elusive. Here, we developed a systematic approach to identify factors involved in heterochromatin silencing at pericentromeres, subtelomeres and the silent mating type locus in Schizosaccharomyces pombe. Using quantitative measures, iterative genetic screening and domain-specific heterochromatin reporters, we identified 369 mutants with different degrees of reduced or enhanced silencing. As expected, mutations in the core heterochromatin machinery globally decreased silencing. However, most other mutants exhibited distinct qualitative and quantitative profiles that indicate heterochromatin domain-specific functions, as seen for example for metabolic pathways affecting primarily subtelomere silencing. Moreover, similar phenotypic profiles revealed shared functions for subunits within complexes. We further discovered that the uncharacterized protein Dhm2 plays a crucial role in heterochromatin maintenance, affecting the inheritance of H3K9 methylation and the clonal propagation of the repressed state. Additionally, Dhm2 loss resulted in delayed S-phase progression and replication stress. Collectively, our systematic approach unveiled a landscape of domain-specific heterochromatin regulators controlling distinct states and identified Dhm2 as a previously unknown factor linked to heterochromatin inheritance and replication fidelity.

Prediction and Elimination of Physiological Tremor During Control of Teleoperated Robot Based on Deep Learning.

Currently, teleoperated robots, with the operator's input, can fully perceive unknown factors in a complex environment and have strong environmental interaction and perception abilities. However, physiological tremors in the human hand can seriously affect the accuracy of processes that require high-precision control. Therefore, this paper proposes an EEMD-IWOA-LSTM model, which can decompose the physiological tremor of the hand into several intrinsic modal components (IMF) by using the EEMD decomposition strategy and convert the complex nonlinear and non-stationary physiological tremor curve of the human hand into multiple simple sequences. An LSTM neural network is used to build a prediction model for each (IMF) component, and an IWOA is proposed to optimize the model, thereby improving the prediction accuracy of the physiological tremor and eliminating it. At the same time, the prediction results of this model are compared with those of different models, and the results of EEMD-IWOA-LSTM presented in this study show obvious superior performance. In the two examples, the MSE of the prediction model proposed are 0.1148 and 0.00623, respectively. The defibrillation model proposed in this study can effectively eliminate the physiological tremor of the human hand during teleoperation and improve the control accuracy of the robot during teleoperation.

Generation of human induced pluripotent stem cell lines derived from patients of cystic biliary atresia

Biliary atresia (BA), resulting from abnormal development of the liver’s internal or external bile ducts, can lead to liver damage and potentially fatal cirrhosis. Type I cystic biliary atresia is a relatively uncommon, but clinically significant variant of BA. It is critical to develop experimental models of BA to examine the etiology and pathogenesis, which remain elusive, and to develop future therapeutics. Here, we have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic BA. These hiPSC lines exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, the clinical significance of which is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in advancing novel therapies for this disease.

A Clinicopathological Study of Scrotal Calcinosis and Literature Review.

Objective. We aimed to investigate the clinicopathological features and pathogenesis of scrotal calcinosis. Methods. Hematoxylin and eosin (HE)-stained slides were performed on 14 patients with scrotal calcinosis, and the clinicopathological characteristics were analyzed together with clinical data. Meanwhile, 81 patients with extrascrotal calcinosis cutis and 7480 patients with epidermoid cysts without calcification in the skin of various parts of the body were collected and analyzed to explore the etiology and pathogenesis of scrotal calcinosis in conjunction with the literature review. Results. All our patients were adult men with a mean age of 38.2 years, with clinical manifestations of multiple scrotal nodules of varying sizes, microscopically characterized by intradermal calcium deposits, of which 3 lesions had a cystic cavity lined with squamous epithelium. Conclusions. Scrotal calcinosis is a rare benign disease that presents clinically as single or multiple hard nodules in the scrotum, usually asymptomatic, and it is histopathologically characterized by intradermal calcium deposition. There is still controversy as to whether it is idiopathic. We believe that scrotal calcinosis is not idiopathic and originates from epidermoid cysts. Prolonged local compression or injury may be one reason for the development of calcification, and perhaps there are other unknown factors contributing to the development of the disease. Surgical excision is the main treatment for this disease with satisfactory therapeutic effectiveness.

The effects of disease lesions and amoxicillin treatment on the physiology of SCTLD-affected corals

Metrics of coral physiology can be used to identify changes in coral health due to environmental stressors or management actions. One of the most unprecedented stressors to Caribbean corals is the spread of stony coral tissue loss disease (SCTLD), which also resulted in the novel management action of in-water amoxicillin treatments on active disease lesions. Though highly effective at halting lesions and preventing coral mortality, possible unintended consequences of topical application of amoxicillin to coral tissue were unknown. We used in-water instrumentation to measure and compare photosynthesis (P), respiration (R), P/R ratios, and calcification of corals that were visually healthy, actively diseased, and diseased but treated with amoxicillin paste. Measurements occurred across three time points and two species – Orbicella faveolata and Montastraea cavernosa. Across all metrics, treatment type did not cause significant differences, indicating that neither SCTLD lesions nor amoxicillin treatments impacted the physiology of adjacent tissues. There were significant variations among time points, which may have resulted from changes to coral health across the reef, variations due to environmental variables, or other unknown factors. We suggest that physiological metrics could be an interesting way to fate track coral health across short- and long-term timeframes. We also conclude that amoxicillin treatments as a tool to halt SCTLD are not detrimental to respiration, photosynthesis, or calcification rates of adult corals.

Atrial Fibrillation in Patients with Very High Risk for Stroke and Adverse Events-Insights from the Observational ARENA Study.

Background: Atrial fibrillation (AF) is a major cause of stroke. An individual risk estimation remains challenging, as AF patients with and without cerebrovascular event (CVE) may differ in yet unknown factors beyond those covered by the CHA2DS2-VASc score. We aimed to identify differences between AF patients with and without CVE with regard to AF characteristics and treatment, vascular risk factors and comorbidities, prognosis and outcome. Methods: We analyzed patients included in the Atrial Fibrillation Rhine-Neckar Region (ARENA) Project, an observational cohort study of patients with AF. Patients were recruited by their general practitioner or during a hospital stay and were divided into two groups for the present analysis: patients with acute CVE at baseline and/or history of CVE versus patients without CVE. Follow-up at 1 year was conducted via phone call. Results: Of 2061 included patients (60.6% male), 292 (14.2%) belonged to the CVE group. Patients in the CVE group were older (mean age 74.6 versus 71.7 years; p < 0.001) and had a higher CHA2DS2-VASc score at baseline (5.3 versus 3.3 points; p < 0.001) based on the preceding CVE. Moreover, patients with either acute or chronic CVE had a larger left atrium (median diameter 47/46 mm versus 44 mm; p = 0.001). Patients with acute CVE had structural heart diseases (p < 0.001) less frequently than patients with previous or without CVE. Mortality at 1 year (HR 1.95; 95%-CI 1.37-2.78) was more frequent in the CVE group (p < 0.001). During 1-year of follow-up, stroke occurred more frequently in survivors with CVE (2.9% versus 0%; p < 0.001). Conclusions: AF patients with CVE have a significantly worse prognosis than AF patients without CVE. Atrial structural remodeling, underlying cardiovascular disease, stroke-induced heart injury and further unidentified factors may account for this finding. Characterization of AF patients including echocardiography to detect atrial structural remodeling may be helpful in risk stratification beyond classical scores.

Adaptive Sliding Mode Control for AUV based on Backstepping and Neural Networks

Abstract Automatic Underwater Vehicle (AUV) inevitably suffers from various interference issues in the marine environment. Due to the limitations of underwater measurement methods and tools, as well as the complexity of AUV's control parameters in the underwater environment, dynamic measurement errors are easily cascaded and amplified, leading to the failure of the control system. In response to this phenomenon, this paper focuses on overcoming the influence of internal and external unknown factors in the tracking and control process of AUV trajectories. The internal factors are mainly the uncertainties generated by the model mismatch problem, and the external factors are mainly from the dynamic ocean currents. The AUV disturbances mainly affect the kinematics and dynamics levels directly or indirectly. In order to achieve the control of internal and external dynamic disturbances, we have designed a control system that employs backstepping (BS) and a sliding mode controller (SMC) with RBF neural networks to achieve the cascaded control of kinematics and dynamics. Comparison of multiple sets of simulations shows that our proposed algorithm has excellent anti-disturbance performance for dynamic conditions with low measurement accuracy.

PDGrad: Guiding Diffusion Model for Reference-Based Blind Face Restoration with Pivot Direction Gradient Guidance.

Reference-based blind face restoration (RefBFR) has gained considerable attention because it utilizes additional reference images to restore facial images in situations where the degradation is caused by unknown factors, making it particularly useful in real-world applications. Recently, guided diffusion models have demonstrated exceptional performance in this task without requiring training. They achieve this by integrating gradients of the losses where each loss reflects the different desired properties of the additional external images. However, these approaches fail to consider potential conflicts between gradients of multiple losses, which can lead to sub-optimal results. To address this issue, we introduce Pivot Direction Gradient guidance (PDGrad), a novel gradient adjustment method for RefBFR within a guided diffusion framework. To this end, we first define the loss function based on both low-level and high-level features. For loss at each feature level, both the coarsely restored image and the reference image are fully integrated. In cases of conflicting gradients, a pivot gradient is established for each level and other gradients are aligned to it, ensuring that the strengths of both images are maximized. Additionally, if the magnitude of the adjusted gradient exceeds that of the pivot gradient, it is adaptively scaled according to the ratio between the two, placing greater emphasis on the pivot. Extensive experimental results on the CelebRef-HQ dataset show that the proposed PDGrad significantly outperforms competitive approaches both quantitatively and qualitatively.

Convolutional neural network augmented soft-sensor for autonomous microfluidic production of uniform bubbles

Microfluidics has emerged as a foundational process for creating highly uniform emulsions and bubbles. To enable integration of microfluidic platforms into industrial processes, achieving precise control over the size uniformity of microfluidic-generated bubbles and emulsions is crucial. Even if the external variables such as flow rates or pressures are kept constant, microfluidic processes can be easily disturbed by unknown factors that would substantially compromise the uniformity of resulting emulsions and bubbles. In this study, we introduce a two-step soft-sensor approach that combines a convolutional neural network (CNN) and an image recognition algorithm for feature extraction to detect both the flow regime and the size and uniformity of resulting bubbles. By using a CNN to detect flow regimes, our controller is able to restore the bubble-producing flow regime in response to disturbances. Beyond self-recovery, our controller actively adjusts to minimize errors, maintain setpoints, mitigate disturbances, and ensure system stability over extended periods. 99.2% of bubbles produced during an 8-hour period remain within 5% of the setpoint with our controller acting. By leveraging the soft sensor and artificial intelligence-assisted feedback control, our work presents a widely applicable approach for precise and automated control of microfluidics in diverse applications.

Natural History of Menstrual Pain and Associated Risk Factors in Early Adolescence

Study ObjectiveTo determine the natural history of menstrual pain without pelvic pathology, the role of progesterone in its pathophysiology, and associated risk factors in a longitudinal study of early post-menarchal girls in North Carolina. MethodsParticipants contributed daily urine samples for up to 3.5 years to measure pregnanediol-3-glucuronide [PdG] (mean 589 urines/participant), completed menstrual diaries, and reported menstrual pain using the Menstrual Symptom Questionnaire (MSQ) biannually. MSQ scores were log-transformed and generalized estimating equations assessed associations with gynecologic age, cycle peak PdG, presumed ovulation, physical activity, anxiety, and depression. Models were adjusted for age at menarche, baseline body mass index, race/ethnicity, parental education and employment, and gynecologic age. ResultsForty-three girls, aged 12.6 ± 1.1 years (mean ± SD) at enrollment with a gynecologic age 0.3 ± 0.2 years, participated. Total MSQ scores were higher for every 1-year increase in gynecologic age (MSQ score ratio: 1.12; 95% CI: 1.08, 1.17; p<0.0001). Overall MSQ (ratio: 1.04; 95% CI: 1.02, 1.06; p=0.0002) and abdominal pain-specific (ratio: 1.04; 95% CI: 1.01, 10.7; p=0.004) scores were higher for every 1000 ng/mg creatinine increase in peak PdG in the preceding cycle. Overall MSQ scores were higher (ratio 1.26; 95% CI: 1.11, 1.44; p=0.0005) if the preceding cycle was presumed ovulatory. Menstrual pain was not associated with physical activity, anxiety, or depression. ConclusionsIn early post-menarchal girls, gynecologic age and PdG were associated with menstrual pain, suggesting a pathophysiologic role for progesterone and other unknown factors in the development of menstrual pain.

Revolutionizing Infertility Management through Novel Peptide-based Targets.

Around 48 million couples and 186 million people worldwide have infertility; of these, approximately 85% have an identifiable cause, the most common being ovulatory dysfunctions, male infertility, polycystic ovary syndrome, and tubule disease. The remaining 15% have infertility for unknown reasons, including lifestyle and environmental factors. The regulation of the hypothalamic- pituitary-adrenal axis (HPA) is crucial for the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which are essential for female reproductive functions. GnRH is the primary reproductive axis regulator. The pattern of GnRH, FSH, and LH release is determined by its pulsatile secretion, which in turn controls endocrine function and gamete maturation in the gonads. Peptides called Kisspeptin (KP), Neurokinin-B (NKB), and Orexin influence both positive and negative feedback modulation of GnRH, FSH, and LH secretion in reproduction. This review article mainly focuses on the historical perspective, isoform, and signaling pathways of KP, NKB, and Orexin novel peptide-based targets including clinical and preclinical studies and having a promising effect in the management of infertility.

Reporting bias, not external focus: A robust Bayesian meta-analysis and systematic review of the external focus of attention literature.

Evidence has ostensibly been accumulating over the past 2 decades suggesting that an external focus on the intended movement effect (e.g., on the golf club during a swing) is superior to an internal focus on body movements (e.g., on your arms during a swing) for skill acquisition. Seven previous meta-studies have all reported evidence of external focus superiority. The most comprehensive of these concluded that an external focus enhances motor skill retention, transfer, and performance and leads to reduced eletromyographic activity during performance and that more distal external foci are superior to proximal external foci for performance. Here, we reanalyzed these data using robust Bayesian meta-analyses that included several plausible models of publication bias. We found moderate to strong evidence of publication bias for all analyses. After correcting for publication bias, estimated mean effects were negligible: g = 0.01 (performance), g = 0.15 (retention), g = 0.09 (transfer), g = 0.06 (electromyography), and g = -0.01 (distance effect). Bayes factors indicated data favored the null for each analysis, ranging from BF01 = 1.3 (retention) to 5.75 (performance). We found clear evidence of heterogeneity in each analysis, suggesting the impact of attentional focus depends on yet unknown contextual factors. Our results contradict the existing consensus that an external focus is always more effective than an internal focus. Instead, focus of attention appears to have a variety of effects that we cannot account for, and, on average, those effects are small to nil. These results parallel previous metascience suggesting publication bias has obfuscated the motor learning literature. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Uncertainty-Aware Health Diagnostics via Class-Balanced Evidential Deep Learning.

Uncertainty quantification is critical for ensuring the safety of deep learning-enabled health diagnostics, as it helps the model account for unknown factors and reduces the risk of misdiagnosis. However, existing uncertainty quantification studies often overlook the significant issue of class imbalance, which is common in medical data. In this paper, we propose a class-balanced evidential deep learning framework to achieve fair and reliable uncertainty estimates for health diagnostic models. This framework advances the state-of-the-art uncertainty quantification method of evidential deep learning with two novel mechanisms to address the challenges posed by class imbalance. Specifically, we introduce a pooling loss that enables the model to learn less biased evidence among classes and a learnable prior to regularize the posterior distribution that accounts for the quality of uncertainty estimates. Extensive experiments using benchmark data with varying degrees of imbalance and various naturally imbalanced health data demonstrate the effectiveness and superiority of our method. Our work pushes the envelope of uncertainty quantification from theoretical studies to realistic healthcare application scenarios. By enhancing uncertainty estimation for class-imbalanced data, we contribute to the development of more reliable and practical deep learning-enabled health diagnostic systems.

Primary hyperoxaluria type 3: from infancy to adulthood in a genetically unique cohort.

Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (HOGA-1) gene. We report the natural history of PH3 in a 16-patient cohort, 15 from a unique genetically isolated population. This retrospective single-center study followed PH3 patients between 2003 and 2023 with demographic, clinical, radiographic, genetic, and biochemical parameters. Genetic population screening was performed in four villages to determine carrier frequency and identify couples at risk in a genetically isolated population. Sixteen patients with biallelic (or homozygous) pathogenic variants (PV) in HOGA-1 (c.944_946 del, c.119C > A, c.208C > T) were included in the study, 15 Druze and one Jewish, aged 0-63years at diagnosis (4 adults and 12 pediatric patients). All symptomatic patients had clinical or imaging signs of nephrolithiasis. One developed chronic kidney disease (CKD) stage 5; biopsy showed focal mesangial sclerosis and chronic tubulo-interstitial changes with few oxalate deposits. Two other patients had CKD stage 2 (eGFR 87 and 74mL/min/1.73m2) upon their last visit. The remaining cohort showed preserved kidney function until the latest follow-up. Of 1167 healthy individuals screened, 90 carriers were found, a rate of 1:13 in the genetically unique cohort screened. A high prevalence of PH3 patients was found among a unique cohort, but probably still underdiagnosed due to relatively mild disease course. The carrier rate is high. There is no specific therapy for PH3, but early diagnosis can prevent redundant diagnostic efforts and provide early treatment for kidney stone disease. Even in our homogeneous cohort, kidney stone disease severity and CKD degree were variable, supporting a suspected contribution of yet unknown genetic or environmental factors.

Right Orchiopexy to Correct Undescended Testicle and Circumcision to Correct Phimosis

Cryptorchidism is a condition in which one or both testicles fail to descend to its normal position in the scrotum. The testicle may reside in the retroperineum, in the internal inguinal ring, in the inguinal canal, or even at the external ring. The exact cause is unknown but several risk factors have been linked to this condition such as premature birth, low birth weight, family history, Down syndrome, alcohol use, and cigarette smoking. Undescended testis occurs in approximately 30% of preterm infants and 1-3% of term infants. Diagnosis is made during examination at birth or shortly thereafter, and timely recognition and management of this condition prevents adverse consequences. The goal of treatment is to relocate the undescended testicle to its proper location in the scrotum. Treatment before 1 year of age lowers the risk of complications such as infertility, testicular cancer, inguinal hernia, and testicular torsion. Treatment can be hormonal, surgical or a combination of both. Hormones such as hCG can sometimes induce descent of the testicle; however, surgery is the preferred option. Orchiopexy is the surgical procedure to free an undescended testicle and implant it in the scrotum. Phimosis is the inability to retract the foreskin covering the glans of the penis. It may appear as a tight ring of the foreskin around the tip of the penis preventing full retraction. Phimosis can be physiologic or pathologic. Physiologic phimosis is seen in children born with tight foreskin at birth and separation occurs naturally overtime while pathologic phimosis is caused by scarring, infection or inflammation. A tight foreskin can interfere with the passage of urine as seen as ballooning of the foreskin during urination. This can lead to inflammation of the penis called balanitis or inflammation of the penis and foreskin called balanoposthitis. Physiologic phimosis does not require intervention and will resolve with daily gentle retraction while pathologic phimosis is treated with topical steroid cream or circumcision. Here we present the case of a young male with an undescended right testicle and phimosis. The right testicle was located in the right inguinal area and was brought down into the scrotum. Circumcision was also done to resolve the phimosis.