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1.
Sci Rep ; 14(1): 16046, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992235

ABSTRACT

With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients. In this paper, the effective range of blasting and the stress distribution under blasting load are analyzed theoretically. The RHT (Riedel-Hiermaier-Thoma) model is used to numerically simulate the blasting process of rock mass with cavity under different ground stress, and the influence of ground stress and lateral pressure coefficient on the crack growth of rock mass is studied. The results show that when there is no ground stress, the damage cracks in rock mass are more concentrated in the horizontal direction and the fracture development tends to the direction where the holes are located, which confirms the guiding effect and stress concentration effect of the holes in rock mass, which helps to promote the crack penetration between the hole and the hole. The length difference of horizontal and vertical damage cracks in rock mass increases with the increase of horizontal and vertical stress difference. Under the same lateral stress coefficient, the larger the horizontal and vertical stress difference is, the stronger the inhibition effect on crack formation is. For blasting of rock mass with high ground stress, the crack formation length between gun holes decreases with the increase of stress level, and the crack extends preferentially in the direction of higher stress. Therefore, the placement of gun holes along the direction of greater stress and the shortening of hole spacing are conducive to the penetration of cracks between gun holes and empty holes. The research can provide reference for rock breaking behavior of deep rock mass blasting.

2.
Int J Biol Macromol ; : 133781, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992528

ABSTRACT

Peptide-major histocompatibility complex (pMHC) multimers are wide recognized as the premier technique for detecting, characterizing, and isolating antigen-specific CD8+ T-cell subsets. These multimers are specifically useful in studying infections, autoimmune conditions, and cancer through single-cell analysis techniques such as flow cytometry and fluorescence microscopy. However, the development of high-throughput assays with commercially available pMHC tetramers can be expensive, while in-house production may pose challenges for most biology research laboratories. In this context, we introduce a cost-friendly and uncomplicated protocol to prepare empty MHC class I tetramers using disulfide-stabilized molecules and photolabile peptide ligands. Our method relies on disulfide bond-stabilized MHC-I molecules, which demonstrated stability when folded into stable monomers in the presence of a photolabile epitope. These monomers, upon ultraviolet irradiation and streptavidin binding, efficiently assemble into tetramers devoid of any peptide. Following a short incubation with the peptide of interest under gentle conditions, the resulting pMHC tetramer effectively detects patient-sourced, neoantigen-specific T cells. Our unique approach streamlines large-scale pMHC generation, thus paving the way for advancements in T cell-based diagnostics and personalized therapies.

3.
Reprod Sci ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958919

ABSTRACT

This study aims to assess the effectiveness of pulsed gonadotropin-releasing hormone (GnRH) micropump replacement therapy in the treatment of hypogonadotropic hypogonadism (HH) caused by primary empty sella (PES).The efficacy of pulsed GnRH replacement therapy using the micropump was evaluated in a middle-aged male patient with HH who had experienced the loss of his only child. Relevant literature was also consulted to compare the differences between pulse GnRH treatment and conventional treatment in terms of the development of secondary sexual characteristics, sex hormone levels, sperm production rate, and sperm activity rate in male patient with HH.In this report, a 45-year-old male diagnosed with HH and PES presented with fatigue and decreased libido. The main characteristics included decreased follicle stimulating hormone (FSH) levels of 0.03 mIU/mL, luteinizing hormone (LH) levels of 0.02 mIU/mL, and testosterone (T) levels of 0.72 nmol/L. Magnetic resonance imaging (MRI) revealed an empty sella. Semen analysis showed a small number of normal sperm with reduced motility. During treatment with the micropump pulse GnRH, the patient experienced no side effects and showed improvements in fatigue, reduced libido, sexual urge, anxiety, and feelings of inferiority. LH, FSH, and T levels returned to normal, while sperm activity rate increased to 79.9%. Ultimately, the patient's spouse achieved a natural pregnancy.Pulsed gonadotropin delivery using the micropump demonstrates good efficacy and tolerability, and aligns more closely with the physiological rhythm of GnRH secretion in the human body.

4.
Intern Emerg Med ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888722

ABSTRACT

The clinical presentation of adrenal insufficiency, a condition causing adrenal hormone deficiency, is characterised by non-specific symptoms and signs: consequently, an important diagnostic delay is often evident which correlates with an increased mortality. This case report shows how the clustering of some symptoms and signs may hamper the diagnostic suspicion for this condition: serum electrolyte alterations and weight loss, when associated to recurrent infections and, in female patients, an empty sella may further guide the clinician towards a diagnosis of adrenal insufficiency. Accordingly, a clinical approach taking into account gender medicine could improve the diagnostic workup.

5.
Front Neurol ; 15: 1365525, 2024.
Article in English | MEDLINE | ID: mdl-38846033

ABSTRACT

Background: The disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world's first case of so-called AVM Pentalogy (AVMP) induced by a AVM. Clinical presentation and result: A 30-year-old female was first seen 9 years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review. Conclusion: During the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus.

6.
Tech Coloproctol ; 28(1): 74, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926191

ABSTRACT

BACKGROUND: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS. METHODS: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle. RESULTS: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%. CONCLUSIONS: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes.


Subject(s)
Pelvic Exenteration , Pelvis , Humans , Pelvic Exenteration/adverse effects , Pelvic Exenteration/methods , Female , Postoperative Complications/etiology , Syndrome , Middle Aged , Omentum/surgery
7.
Foods ; 13(12)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38928760

ABSTRACT

Rural residents in China are still at risk of malnutrition, and increasing dietary diversity is crucial to improving their health. This study empirically analyzed the impact of non-farm employment on the dietary diversity of rural left-behind family members based on the China Land Economy Survey (CLES) 2020-2021 panel data at the farm and village levels. Dietary diversity was measured using the dietary diversity score (DDS) and the Chinese Food Guide Pagoda Score (CFGPS). The empirical results show that non-farm employment significantly enhances the dietary diversity of rural left-behind household members, including animal food diversity and plant food diversity. This result verifies the altruism phenomenon of non-farm employment in family diet. Mechanism analysis shows that non-farm employment enhances the dietary diversity of rural left-behind family members by increasing the level of family income, Internet accessibility, and family education. Heterogeneity analysis shows that non-farm employment does not enhance the dietary diversity of rural empty nesters and even has a negative impact. This reminds us that the nutritional health of rural empty nesters needs attention in the context of rapid urbanization and aging.

8.
Article in English | MEDLINE | ID: mdl-38908134

ABSTRACT

The field of recombinant adeno-associated virus (rAAV) gene therapy has attracted increasing attention over decades. Within the ongoing challenges of rAAV manufacturing, the co-production of impurities, such as empty and partial capsids containing no or truncated transgenes, poses a significant challenge. Due to their potential impact on drug efficacy and clinical safety, it is imperative to conduct comprehensive monitoring and characterization of these impurities prior to the release of the final gene therapy product. Nevertheless, existing analytical techniques encounter notable limitations, encompassing low throughput, long turnaround times, high sample consumption, and/or complicated data analysis. Chromatography-based analytical methods are recognized for their current Good Manufacturing Practice (cGMP) alignment, high repeatability, reproducibility, low limit of detection, and rapid turnaround times. Despite these advantages, current anion exchange high pressure liquid chromatography (AEX-HPLC) methods struggle with baseline separation of partial capsids from full and empty capsids, resulting in inaccurate full-to-empty capsid ratio, as partial capsids are obscured within peaks corresponding to empty and full capsids. In this study, we present a unique analytical AEX method designed to characterize not only empty and full capsids but also partial capsids. This method utilizes continuous N-Rich chromatography with recycling between two identical AEX columns for the accumulation and isolation of partial capsids. The development process is comprehensively discussed, covering the preparation of reference materials representing full (rAAV-LacZ), partial (rAAV-GFP), and empty (rAAV-empty) capsids, N-rich method development, fraction analysis, determination of fluorescence response factors between capsid variants, and validation through comparison with other comparative techniques.


Subject(s)
Capsid , Dependovirus , Dependovirus/genetics , Dependovirus/isolation & purification , Chromatography, Ion Exchange/methods , Capsid/chemistry , Chromatography, High Pressure Liquid/methods , Reproducibility of Results
9.
Front Public Health ; 12: 1239445, 2024.
Article in English | MEDLINE | ID: mdl-38868161

ABSTRACT

Aim: This study aims to verify the effectiveness of M-O-A telenursing intervention model in improving the health status and quality of life of the empty-nest older adult individuals with chronic diseases by a randomized comparative trial. Methods: M-O-A telenursing intervention model was constructed based on the needs of the participants. The control group (N = 39) received routine nursing, the experimental group (N = 39) received M-O-A telenursing intervention in addition to routine nursing. After 12 weeks of intervention, the intervention effects of being a participant in the two groups were evaluated. SPSS 26.0 was used for data analysis. Results: After 12 weeks of intervention, for the experimental group, each dimension of quality of life based on EQ-5D-3L became better, especially for "pain/discomfort," "anxiety/depression," "HRQoL" and "EQ-VAS" (all p < 0.05) and each dimension of quality of life based on SF-36 became better too, especially for "GH," "BP," "RE," "MH," "VT," "SF," "PCS," "MCS," "SF-36" (all p < 0.05). In addition, there was a statistical downward trend in blood pressure, blood glucose, weight, BMI, fat rate, nap duration, number of nocturnal awakenings, light sleep rate and a statistical upward trend in water rate, basal metabolic rate, nighttime sleep duration, deep sleep rate, rapid eye movement sleep rate, especially at the end of intervention (all p < 0.05). While for the control group, there was no statistical improvement in all these aspects. Conclusion: The M-O-A telenursing model could effectively regulate quality of life and health condition of the empty-nest older adult individuals with chronic diseases, making it worthy of further promotion and application.


Subject(s)
Quality of Life , Humans , Male , Female , Aged , Chronic Disease , Health Status , Middle Aged , Surveys and Questionnaires , Telemedicine , Aged, 80 and over
10.
Int J Colorectal Dis ; 39(1): 79, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797803

ABSTRACT

BACKGROUND: Empty Pelvis Syndrome, subsequent to the removal of pelvic organs, results in the descent of the small bowel into an inflamed pelvic cavity, leading to the formation of adhesions and subsequent small bowel obstruction. However, no effective measures have been previously described. OBJECTIVE: Describe a simple and autologous solution to prevent "Empty Pelvis Syndrome," small bowel obstruction, and adhesions by utilizing the cecum to occlude the pelvis. DESIGN: Mobilization of the right colon to lower the cecum into the pelvic cavity to occlude the superior pelvic ring to some degree and changing the direction of the terminal ileum. SETTINGS: Hospital Universitario Fundación Jiménez Díaz, Department of General Surgery, Colorectal Service. PATIENTS: Eight anonymized patients were included in this study, each with varying colorectal pathologies. Patients were above 18 years old. MAIN OUTCOME MEASURES: Percent of blockage of the superior pelvic ring produced by the descended cecum recorded in percentage; the amount of small intestine descended past the superior pelvic ring recorded in cm. RESULTS: The mobilization of the cecum achieved partial occlusion of the superior pelvic ring. The descent of the small bowel beyond this landmark ranged from 0 to 4.9 cm. LIMITATIONS: Given the small number of patients included in this study, these results cannot be generalized to the whole of the population. A bladder emptying protocol prior to CT scans was not implemented, resulting in variations in measurements among patients. CONCLUSION: The cecum-to-pelvis technique is a simple method that can serve as an autologous solution to EPS (enteropelvic fistula) and help reduce postoperative complications such as SBO (small bowel obstruction) and adhesions. It is not essential to completely occlude the superior pelvic ring to achieve successful outcomes.


Subject(s)
Cecum , Pelvis , Postoperative Complications , Humans , Cecum/surgery , Pelvis/surgery , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Female , Male , Middle Aged , Tissue Adhesions/prevention & control , Tissue Adhesions/etiology , Adult , Intestinal Obstruction/prevention & control , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Aged
11.
Hum Gene Ther ; 35(11-12): 401-411, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38717948

ABSTRACT

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and high sedimentation coefficient substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF (high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the relative standard deviation (RSD) could be within 5%. Even for empty or partially less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4 × 1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235 nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Because of the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control) laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.


Subject(s)
Dependovirus , Genetic Vectors , Ultracentrifugation , Dependovirus/genetics , Ultracentrifugation/methods , Humans , Genetic Vectors/genetics , Genetic Vectors/chemistry , Calibration , Genetic Therapy/methods , Capsid/chemistry , HEK293 Cells
12.
Water Environ Res ; 96(5): e11035, 2024 May.
Article in English | MEDLINE | ID: mdl-38761092

ABSTRACT

One alternative adsorbent (AA) and five ion exchange (IX) resins were tested for the removal of per- and polyfluoroalkyl substances (PFAS) from groundwater in pilot-scale columns for up to 19 months using empty bed contact times (EBCTs) representative of full-scale treatment. For the six detected PFAS in the pilot feed water, the long-chain PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], and perfluorohexanesulfonic acid [PFHxS]) were well removed with only PFOA, which is a perfluoroalkyl carboxylic acid (PFCA) eventually breaking through as the media became exhausted. Perfluorobutanesulfonic acid (PFBS), a short-chain perfluorosulfonic acid (PFSA), was also well removed, whereas short-chain PFCAs (perfluoropentanoic acid [PFPeA] and perfluorobutanoic acid [PFBA]) were not removed (i.e., immediate breakthrough). Overall, IX and AA demonstrated superior removal of PFSAs compared to PFCAs (i.e., later breakthrough of PFSAs translating to longer media life). Media life varied, ranging from 6 to 15 months before adsorbents reached a significant PFOA breakthrough. The performance of the two adsorbents piloted at shorter EBCT reasonably predicted the longer (representative) pilot EBCT results (within ±20-30%) for the same adsorbents following data scaling. This suggests that pilot-scale testing may be conducted at a faster pace and therefore more economically. PRACTITIONER POINTS: Long-chain PFAS (PFOA, PFOS, and PFHxS) were well removed by five ion exchange and one alternative adsorbent tested herein. One short-chain PFAS (PFBS) was well removed with no removal of two other short-chain PFAS (PFBA and PFPeA). Performance of the two adsorbents piloted at shorter EBCT reasonably predicted the longer (representative) pilot EBCT results for the same adsorbents following data scaling.


Subject(s)
Fluorocarbons , Water Pollutants, Chemical , Water Purification , Fluorocarbons/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Pilot Projects , Water Purification/methods
13.
Biotechnol Bioeng ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807330

ABSTRACT

Recombinant adeno-associated virus, serotype 9 (rAAV9) has shown promise as a gene therapy vector for muscle and central nervous diseases. High-dose requirements of these therapies present critical safety considerations and biomanufacturing challenges. Notably, the reduction of empty capsids (ECs), which lack therapeutic transgene, from rAAV9 products is critical to maximize efficacy. Removal of rAAV ECs from full capsids is a major downstream challenge because of their highly similar biophysical characteristics. Ultracentrifugation (UC) reduces ECs but is laborious and difficult to scale. In this paper, to replace a poorly scalable UC process, we developed an anion exchange (AEX) chromatography for rAAV9 EC reduction from full capsids. AEX load preparation by dilution incurred major product loss. The addition of histidine and surfactants to dilution buffers increased yield and reduced aggregation. Elution salts were screened and sodium acetate was found to maximize yield and EC reduction. The most promising load dilution buffer and elution salt were used in combination to form an optimized AEX method. The process reduced ECs three-fold, demonstrated robustness to a broad range of EC load challenges, and was scaled for large-scale manufacture. Compared to UC, the AEX method simplified scale-up, reduced ECs to comparable levels (20%), afforded similar purity and product quality, and increased yield by 14%.

14.
Carbohydr Polym ; 338: 122194, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38763709

ABSTRACT

The rising demand for food packaging has led to a growing interest in sustainable and eco-friendly food coatings. Carboxymethyl cellulose (CMC), being a versatile cellulose derivative produced from various lignocellulosic sources, has emerged in edible food coatings. This review evaluates the research trends on CMC production from empty fruit bunch (EFB) as a potential edible food coating material by systematic review approach. It explores sustainable pre-treatment for green cellulose and different CMC synthesis methods. The review compares CMC-based coatings to other materials, focusing on formulation processes, coating quality, safety, and commercial feasibility. The bibliometric analysis is performed to correlate food coating and CMC. As a result, the study discovered the rapid growth in research on edible food coatings made from CMC for various food industry applications. The green approach such as ozone pre-treatment appear as promising method for cellulose isolation from EFB to be used as raw material for CMC. The synthesis conditions of the treatment would affect the CMC characteristics and usage. Herein, utilizing CMC from cellulose EFB in coating formulation and on coated food shows different benefits. This review provides a road map for future research with potential to make important contributions to the food industry's long-term evolution.


Subject(s)
Food Packaging , Fruit , Fruit/chemistry , Carboxymethylcellulose Sodium/chemistry , Cellulose/chemistry
15.
J Aging Soc Policy ; : 1-17, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38734983

ABSTRACT

Evidence to date has been inconclusive on the effects of public pension on family support to older adults, and the underlying mechanism behind such effects remains unclear. This study examines the effects of the New Rural Social Pension Scheme on family support to empty-nest older parents in rural China, where family care is traditionally favored for older adults. Using data from the China Longitudinal Aging Social Survey, the findings reveal that pension receipt promotes bidirectional financial transfers and intimate relationships between generations, thus increasing (or crowding in) children's financial and care support to their empty-nest parents. On the other hand, receiving pensions may discourage parental care support to children and partially decrease (or crowd out) children's financial and care support. This crowding-out effect, however, is limited and thus insufficient for counteracting the crowding-in effects from other pathways. Overall, these findings indicate that national welfare, such as pensions, can encourage family support through inter-generational contracts and intimacy, strengthening familial bonds and facilitating mutual assistance within families. For policy implications, government should prioritize improving benefit levels of public pensions to harness the caregiving potential of families and providing essential services that assist families in addressing care burdens.

16.
Eur J Obstet Gynecol Reprod Biol ; 297: 221-226, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38691974

ABSTRACT

OBJECTIVE(S): Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved in an IVF cycle despite apparently normal follicular development and meticulous follicular aspiration following ovulation induction. The EFS is called genuine (gEFS) when the trigger administration is correct. The existence of gEFS is a subject of controversy, and it is quite rare with an undetermined etiology. Genetic defects in specific genes have been demonstrated to be responsible for this condition in some patients. Our objective was to identify novel genetic variants associated with gEFS. STUDY DESIGN: We conducted a prospective observational study including 1,689 egg donors from July 2017 to February 2023. WES were performed in patients suffering gEFS. RESULTS: Only 7 patients (0.41 %) exhibited gEFS after two ovarian stimulation cycles and we subsequently performed whole exome sequencing (WES) on these patients. Following stringent filtering, we identified 6 variants in 5 affected patients as pathogenic in new candidate genes which have not been previously associated with gEFS before, but which are involved in important biological processes related to folliculogenesis. These genetic variants included c.603_618del in HMMR, c.1025_1028del in LMNB1, c.1091-1G > A in TDG, c.607C > T in HABP2, c.100 + 2 T > C in HAPLN1 and c.3592_3593del in JAG2. CONCLUSION: As a conclusion, we identified new candidate genes related to gEFS that expand the mutational spectrum of genes related to gEFS.This study show that WES might be an efficient tool to identify the genetic etiology of gEFS and provide further understanding of the pathogenic mechanism of gEFS.


Subject(s)
Exome Sequencing , Ovarian Follicle , Humans , Female , Adult , Prospective Studies , Ovulation Induction , Ovarian Diseases/genetics
17.
Bioprocess Biosyst Eng ; 47(6): 877-890, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703202

ABSTRACT

Ultracentrifugation is an attractive method for separating full and empty capsids, exploiting their density difference. Changes of the serotype/capsid, density of loading material, or the genetic information contained in the adeno-associated viruses (AAVs) require the adaptation of the harvesting parameters and the density gradient loaded onto the centrifuge. To streamline these adaptations, a mathematical model could support the design and testing of operating conditions.Here, hybrid models, which combine empirical functions with artificial neural networks, are proposed to describe the separation of full and empty capsids as a function of material and operational parameters, i.e., the harvest model. In addition, critical quality attributes are estimated by a quality model which is operating on top of the harvest model. The performance of these models was evaluated using test data and two additional blind runs. Also, a "what-if" analysis was conducted to investigate whether the models' predictions align with expectations.It is concluded that the models are sufficiently accurate to support the design of operating conditions, though the accuracy and applicability of the models can further be increased by training them on more specific data with higher variability.


Subject(s)
Dependovirus , Ultracentrifugation , Dependovirus/genetics , Dependovirus/isolation & purification , Ultracentrifugation/methods , Virion/isolation & purification , Virion/chemistry , Neural Networks, Computer
18.
Diagnostics (Basel) ; 14(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38732300

ABSTRACT

Empty nose syndrome (ENS) is a complex condition characterized by symptoms such as dyspnea, nasal discomfort, and emotional challenges. This study aimed to evaluate functional exercise capacity and perceived exertion in patients with ENS. Patients with ENS who presented with a range of severe symptoms were prospectively enrolled. Pulmonary function was evaluated using spirometry, and functional exercise capacity was measured via the 6 min walk test (6-MWT). Perceived exertion was quantified using the Borg scale, and cardiopulmonary function was evaluated by monitoring peripheral oxygen saturation (SpO2). These parameters were assessed before and after nasal reconstruction surgery. A total of 44 patients with ENS were enrolled and classified into mild-to-moderate (n = 20) and severe (n = 24) symptom groups. Spirometry results showed no significant differences before and after surgery in the entire cohort. Perceived exertion showed significant postoperative improvement (p = 0.006). The severe ENS symptom group experienced significant improvement in SpO2 (p = 0.013) and perceived exertion (p = 0.002) at the end of the 6-MWT after surgery. Surgical intervention significantly enhanced functional exercise capacity (p = 0.038) in patients with mild-to-moderate ENS symptoms. Surgical reconstruction positively affected perceived exertion and SpO2 at the end of the 6-MWT in patients with ENS. The severity of ENS symptoms, as assessed by SNOT-25 scores, influenced these outcomes. These findings underscore the potential benefits of surgical intervention for enhancing exercise tolerance and respiratory efficiency.

19.
Neuroradiology ; 66(7): 1161-1176, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38676750

ABSTRACT

PURPOSE: Intracranial hypertension (IH) frequently complicates cerebral venous thrombosis (CVT). Distinct neuroimaging findings are associated with IH, yet their discriminative power, reversibility and factors favoring normalization in prospective CVT patients are unknown. We determined test performance measures of neuroimaging signs in acute CVT patients, their longitudinal change under anticoagulation, association with IH at baseline and with recanalization at follow-up. METHODS: We included 26 consecutive acute CVT patients and 26 healthy controls. Patients were classified as having IH based on CSF pressure > 25 cmH2O and/or papilledema on ophthalmological examination or ocular MRI. We assessed optic nerve sheath diameter (ONSD), optic nerve tortuousity, bulbar flattening, lateral and IVth ventricle size, pituitary configuration at baseline and follow-up, and their association with IH and venous recanalization. RESULTS: 46% of CVT patients had IH. ONSD enlargement > 5.8 mm, optic nerve tortuousity and pituitary grade ≥ III had highest sensitivity, ocular bulb flattening and pituitary grade ≥ III highest specificity for IH. Only ONSD reliably discriminated IH at baseline. Recanalization was significantly associated with regressive ONSD and pituitary grade. Other neuroimaging signs tended to regress with recanalization. After treatment, 184.9 ± 44.7 days after diagnosis, bulbar flattening resolved, whereas compared with controls ONSD enlargement (p < 0.001) and partially empty sella (p = 0.017), among other indicators, persisted. CONCLUSION: ONSD and pituitary grading have a high diagnostic value in diagnosing and monitoring CVT-associated IH. Given their limited sensitivity during early CVT and potentially persistent alterations following IH, neuroimaging indicators can neither replace CSF pressure measurement in diagnosing IH, nor determine the duration of anticoagulation.


Subject(s)
Intracranial Hypertension , Intracranial Thrombosis , Venous Thrombosis , Humans , Male , Female , Intracranial Hypertension/diagnostic imaging , Adult , Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/complications , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/complications , Sensitivity and Specificity , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Middle Aged , Case-Control Studies , Prospective Studies
20.
J Allergy Clin Immunol Pract ; 12(6): 1462-1471, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677589

ABSTRACT

Nasal obstruction is the subjective perception and objective state of insufficient airflow through the nose. Nasal congestion, conversely, describes a state of not just inadequate airflow or obstructive phenomena but also pressure- and mucus-related states to the patient. Nasal receptors belonging to the transient receptor potential (TRP) protein family mediate the sense of nasal patency via the trigeminal nerve. The transient receptor potential melastatin-8 (TRPM8) responds to temperatures around 8°C to 22°C, and is stimulated by menthol and other cooling agents. The radiant effects of airflow create heat loss to activate these receptors and humans perceive this as nasal patency rather than the direct detection of airflow. The thermovascular state of the mucosa, in conditions such as rhinitis, influence TRPM8 activation. Nasal endoscopy can show signs of rhinitis and should be considered an essential part of the workup of nasal congestion. Efforts to relieve nasal congestion need to manage the mucosal state and surgery needs to ensures that the nasal cavity mucosa is exposed to the cooling effects of airflow rather than simply creating a passage to the nasopharynx.


Subject(s)
Nasal Mucosa , Nasal Obstruction , Humans , Nasal Obstruction/diagnosis , Nasal Mucosa/metabolism , TRPM Cation Channels/metabolism , Endoscopy , Rhinitis/diagnosis , Rhinitis/physiopathology
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