Periodic Flows in Microfluidics.

Microfluidics, the science and technology of manipulating fluids in microscale channels, offers numerous advantages, such as low energy consumption, compact device size, precise control, fast reaction, and enhanced portability. These benefits have led to applications in biomedical assays, disease diagnostics, drug discovery, neuroscience, and so on. Fluid flow within microfluidic channels is typically in the laminar flow region, which is characterized by low Reynolds numbers but brings the challenge of efficient mixing of fluids. Periodic flows are time-dependent fluid flows, featuring repetitive patterns that can significantly improve fluid mixing and extend the effective length of microchannels for submicron and nanoparticle manipulation. Besides, periodic flow is crucial in organ-on-a-chip (OoC) for accurately modeling physiological processes, advancing disease understanding, drug development, and personalized medicine. Various techniques for generating periodic flows have been reported, including syringe pumps, peristalsis, and actuation based on electric, magnetic, acoustic, mechanical, pneumatic, and fluidic forces, yet comprehensive reviews on this topic remain limited. This paper aims to provide a comprehensive review of periodic flows in microfluidics, from fundamental mechanisms to generation techniques and applications. The challenges and future perspectives are also discussed to exploit the potential of periodic flows in microfluidics.

Computational modeling of light processing in the habenula and dorsal raphe based on laser ablation of functionally-defined cells.

BACKGROUND: The habenula is a major regulator of serotonergic neurons in the dorsal raphe, and thus of brain state. The functional connectivity between these regions is incompletely characterized. Here, we use the ability of changes in irradiance to trigger reproducible changes in activity in the habenula and dorsal raphe of zebrafish larvae, combined with two-photon laser ablation of specific neurons, to establish causal relationships. RESULTS: Neurons in the habenula can show an excitatory response to the onset or offset of light, while neurons in the anterior dorsal raphe display an inhibitory response to light, as assessed by calcium imaging. The raphe response changed in a complex way following ablations in the dorsal habenula (dHb) and ventral habenula (vHb). After ablation of the ON cells in the vHb (V-ON), the raphe displayed no response to light. After ablation of the OFF cells in the vHb (V-OFF), the raphe displayed an excitatory response to darkness. After ablation of the ON cells in the dHb (D-ON), the raphe displayed an excitatory response to light. We sought to develop in silico models that could recapitulate the response of raphe neurons as a function of the ON and OFF cells of the habenula. Early attempts at mechanistic modeling using ordinary differential equation (ODE) failed to capture observed raphe responses accurately. However, a simple two-layer fully connected neural network (NN) model was successful at recapitulating the diversity of observed phenotypes with root-mean-squared error values ranging from 0.012 to 0.043. The NN model also estimated the raphe response to ablation of D-off cells, which can be verified via future experiments. CONCLUSION: Lesioning specific cells in different regions of habenula led to qualitatively different responses to light in the dorsal raphe. A simple neural network is capable of mimicking experimental observations. This work illustrates the ability of computational modeling to integrate complex observations into a simple compact formalism for generating testable hypotheses, and for guiding the design of biological experiments.

The physiology and pharmacology of oxytocin in labor and in the peripartum period.

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta.

Development of 3D-Printed Two-Compartment Capsular Devices for Pulsatile Release of Peptide and Permeation Enhancer.

OBJECTIVE: The oral absorption of a peptide is driven by a high local concentration of a permeation enhancer (PE) in the gastrointestinal tract. We hypothesized that a controlled release of both PE and peptide from a solid formulation, capable of maintaining an effective co-localized concentration of PE and peptide could enhance oral peptide absorption. In this study, we aimed to develop a 3D-printed two-compartment capsular device with controlled pulsatile release of peptide and sodium caprate (C10). METHODS: 3D-printed two-compartment capsular device was fabricated using a fused deposition modeling method. This device was then filled with LY peptide and C10. The release profile was modulated by changing the thickness and polymer type of the capsular device. USP apparatus II dissolution test was used to evaluate the impacts of device thickness and polymer selection on release profile in vitro. An optimal device was then enteric coated with HPMCAS. RESULTS: A strong linear relationship between the thickness of capsular devices and the delay in the release onset time was observed. An increase in the device thickness or the use of PLA decreased the release rate. The capsular device with compartment 1, compartment 2 and fence thickness of 0.4; 0.95 and 0.5 mm, respectively, and the use of PVA achieved desired pulsatile release profiles of both peptide and C10. Furthermore, enteric-coated capsular devices with HPMCAS had similar pulsatile release profiles compared to non-enteric coated devices. CONCLUSION: These findings suggest potential application of 3D-printing techniques in the formulation development for complex modified drug release products.

Pulsatile Gonadotropin-Releasing Hormone Therapy Is Associated With Better Spermatogenic Outcomes than Gonadotropin Therapy in Patients With Pituitary Stalk Interruption Syndrome.

OBJECTIVE: To compare the effects of combined gonadotropin and pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). METHODS: Male patients with PSIS (N = 119) were retrospectively studied. Patients received pulsatile GnRH therapy (N = 59) were divided into response and poor-response groups based on luteinizing hormone (LH) levels after 1-month treatment with a cutoff value of 1 or 2 IU/L. Participants with gonadotropin therapy were divided into human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) group (N = 60), and patients with pulsatile GnRH therapy were classified into GnRH group (N = 28) with treatment duration ≥6 months. RESULTS: The overall success rates of spermatogenesis for hMG/hCG and GnRH therapy were 51.67% (31/60) vs 33.90% (20/59), respectively. GnRH group required a shorter period to induce spermatogenesis (8 vs 15 months, P = .019). hMG/hCG group had higher median total testosterone than GnRH group [2.16, interquartile range(IQR) 1.06-4.89 vs 1.31, IQR 0.21-2.26 ng/mL, P = .004]. GnRH therapy had a beneficial effect on spermatogenesis compared to hMG/hCG therapy (hazard ratio 1.97, 95% confidence interval 1.08-3.57, P = .026). In patients with pulsatile GnRH therapy, compared with the poor-response group, the response group had a higher successful spermatogenesis rate (5.00% vs 48.72%, P = .002) and higher median basal total testosterone (0.00, IQR 0.00-0.03 vs 0.04, IQR 0.00-0.16 ng/mL, P = .026) with LH = 1 IU/L as the cutoff value after 1-month pulsatile GnRH therapy. CONCLUSIONS: Pulsatile GnRH therapy was superior to hMG/hCG therapy for spermatogenesis in patients with PSIS. Earlier spermatogenesis and higher concentrations of sperm could be obtained in the GnRH group if patients received therapy over 6 months.

Monitoring Berlin Heart EXCOR by computer vision: A preliminary implementation and evaluation.

BACKGROUND: EXCOR Pediatric is one of the most commonly used ventricular assist devices (VAD) for small children; it requires visual inspection of the diaphragm movement to assess its operating status. Although this visual inspection can only be performed by trained medical professionals, it can also be attempted by the recent advances in computer vision technology. METHODS: Movement of the diaphragm in the operating EXCOR VAD was recorded as movies and annotated frame-by-frame in three classes according to the state of the diaphragm: "fill," "mid," and "empty." Three models, MobileNetV3, EfficientNetV2, and MobileViT, were trained using the frames, and their performance was evaluated based on the accuracy and area under the receiver operating characteristic curve (AROC). RESULTS: A total of 152 movies were available from two participants. Only the 10 mL pumps were used. Ninety-eight movies were used for annotation and frame extraction, and 7949 frames per class were included in the analysis. The macro-average accuracies of the three models were 0.88, 0.91, and 0.93, and the AROC were 0.99, 0.98, and 0.99 for MobileNetV3, EfficientNetV2, and MobileViT, respectively. CONCLUSION: Image recognition models based on lightweight deep neural networks could detect the diaphragm state of EXCOR VAD with sufficient accuracy, although there were limited variations in the dataset. This suggests the potential of computer vision for the automated monitoring of the EXCOR diaphragm position.

Evaluation of extra-corporeal membrane oxygenator cannulae in pulsatile and non-pulsatile pediatric mock circuits.

BACKGROUND: This study evaluated the hemodynamic performance of arterial and venous cannulae in a compliant pediatric extracorporeal membrane oxygenation (ECMO) mock circuit in pulsatile and non-pulsatile flow conditions. METHODS: The ECMO setup consisted of an oxygenator, diagonal pump, and standardized-length arterial/venous tubing with pressure transducers. A validated left-heart mock loop was adapted to simulate pediatric conditions. The pulsatile flow was driven by a computer-controlled piston pump set at 120 bpm. A roller pump was used for non-pulsatile conditions. The circuit was primed with 40% glycerol-based solution. The cardiac output was set to 1 L/min and the aortic pressure to 40-50 mmHg. Four arterial cannulae (8Fr, 10Fr, 12Fr, 14Fr) and five venous cannulae (12Fr, 14Fr, 16Fr, 18Fr, 20Fr) (Medtronic, Inc., Minneapolis, MN, USA) were tested at increasing flow rate in 12 combinations. RESULTS: The pulsatile condition required lower ECMO pump speeds for all cannulae combinations at a given flow rate, inducing a significantly smaller increase of flow in the mock loop. Under non-pulsatile conditions, the aortic and arterial pressures in the cannulae were higher (p < 0.01) while no significant differences in pressure drop and pressure-flow characteristics (M-number) were observed. The total hemodynamic energy was higher in case of non-pulsatile flow (p < 0.01). CONCLUSION: Under non-pulsatile conditions, the system was characterized by overall higher pressures, resulting in higher support to the patient. The consequent increase of potential energy compensates for increases of kinetic energy, leading to a higher total hemodynamic energy. Pressure gradients and M number are independent of the testing conditions. Pulsatile testing conditions led to more physiological testing conditions, and it is recommended for ECMO testing.

Pulsatile Tinnitus: Differential Diagnosis and Approach to Management.

PURPOSE OF REVIEW: The purpose of this review is to provide an updated approach to the evaluation and management of pulsatile tinnitus (PT), an uncommon but often treatable subtype of tinnitus. RECENT FINDINGS: Secondary PT can be due to either vascular or non-vascular etiologies, including, but not limited to: neoplasm, arteriovenous malformation or fistula, idiopathic intracranial hypertension, dural venous sinus stenosis, otoacoustic etiologies (e.g., otosclerosis, patulous eustachian tube) and bony defects (e.g., superior semicircular canal dehiscence). Computed tomography (CT) and magnetic resonance imaging (MRI) imaging have comparable diagnostic yield, though each may be more sensitive to specific etiologies. If initial vascular imaging is negative and a vascular etiology is strongly suspected, digital subtraction angiography (DSA) may further aid in the diagnosis. Many vascular etiologies of PT can be managed endovascularly, often leading to PT improvement or resolution. Notably, venous sinus stenting is an emerging therapy for PT secondary to idiopathic intracranial hypertension with venous sinus stenosis. Careful history and physical exam can help establish the differential diagnosis for PT and guide subsequent evaluation and management. Additional studies on the efficacy and long-term outcome of venous sinus stenting for venous stenosis are warranted.

Greater sphenoid wing reconstruction with 3D printed anatomical intracranial implant for a child with spheno-orbital encephalocele.

Sphenoid wing dysplasia is a characteristic finding in children with neurofibromatosis type 1 (NF1). Some of these children develop proptosis and vision loss secondary to the spheno-orbital encephalocele. A 6-year-old boy presented to us with complaints of painless progressive uni-ocular vision loss and progressive pulsatile proptosis. Imaging revealed spheno-orbital encephalocele into the orbit through the dysplastic posterior orbital wall. 3D printed customized implant was designed and placed to fit the defect. This prevented further herniation of the temporal lobe into the orbit, leading to reduction of proptosis and improvement in vision of the child.

Transient Performance Analysis of Centrifugal Left Ventricular Assist Devices Coupled With Windkessel Model: Large Eddy Simulations Study on Continuous and Pulsatile Flow Operation.

Computational fluid dynamics (CFD) simulations are widely used to develop and analyze blood-contacting medical devices such as left ventricular assist devices (LVADs). This work presents an analysis of the transient behavior of two centrifugal LVADs with different designs: HeartWare VAD and HeartMate3. A scale-resolving methodology is followed through Large Eddy Simulations, which allows for the visualization of turbulent structures. The three-dimensional (3D) LVAD models are coupled to a zero-dimensional (0D) 2-element Windkessel model, which accounts for the vascular resistance and compliance of the arterial system downstream of the device. Furthermore, both continuous- and pulsatile-flow operation modes are analyzed. For the pulsatile conditions, the artificial pulse of HeartMate3 is imposed, leading to a larger variation of performance variables in HeartWare VAD than in HeartMate3. Moreover, CFD results of pulsatile-flow simulations are compared to those obtained by accessing the quasi-steady maps of the pumps. The quasi-steady approach is a predictive tool used to provide a preliminary approximation of the pulsatile evolution of flow rate, pressure head, and power, by only imposing a speed pulse and vascular parameters. This preliminary quasi-steady solution can be useful for deciding the characteristics of the pulsatile speed law before running a transient CFD simulation, as the former entails a significant reduction in computational cost in comparison to the latter.

Blood Flow of the Infraspinatus Muscle in Individuals With and Without Shoulder Pain and Myofascial Trigger Points: A Color Doppler Ultrasound and Reliability Study.

OBJECTIVES: Myofascial trigger points (MTrPs) are potential contributors to shoulder pain and can lead to local ischemia and hypoxia, thus causing pain. Color Doppler ultrasound (US) has been used to examine the vascular environment around MTrPs, but has not been used to examine blood flow impairments in patients with shoulder pain and MTrPs. The reliability of color Doppler US for measuring infraspinatus muscle blood flow also has not been established. This study aimed to investigate differences in blood flow between individuals with and without shoulder pain and the reliability of Doppler US for measuring infraspinatus muscle blood flow. METHODS: Forty participants were enrolled, 20 with shoulder pain and MTrPs and 20 without. Color Doppler US examination was performed twice on each participant to measure peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and pulsatile index (PI) of the infraspinatus muscle. RESULTS: The symptomatic participants had significantly higher PSV (ie, impaired blood flow) than the asymptomatic participants. There were no significant between-group differences in EDV, RI, and PI. The results also demonstrated good-to-excellent intra-rater reliability for color Doppler US measurements of PSV, EDV, RI, and PI for both groups. CONCLUSION: This study demonstrated differences in blood flow near MTrPs in the infraspinatus muscle between individuals with and without shoulder pain. It also established good-to-excellent reliability of color Doppler US in measuring infraspinatus muscle blood flow. These findings suggest color Doppler US is a useful tool to identify vascular impairments for shoulder pain associated with MTrPs.

Eumelanin and Pheomelanin Modelling in Optical Oximetry Using Pulse Oximetry (for 540 nm and 660 nm): DC Component.

Oximetry is used to quantify the presence of oxygen in soft tissues. It can be expressed as, for example, tissue oxygen saturation (StO2), arterial oxygen saturation (SaO2) and pulsatile oxygen saturation (SpO2), among others. Non-invasive medical devices are used to estimate (SaO2). Their accuracy is compromised in individuals with highly pigmented skin. The aim of this initial work is to go back few steps into the understanding of the light absorption for the DC component in pulse oximeters, by using a mixtures model for different hypothetical scenarios of normoxia and hyperoxia. Under hypoxic states, an initial and simple multi-wavelength approach could be established to identify the impact of eumelanin (EuM) and pheomelanin (PhM), which are directly related to skin pigmentation in dark skin colour individuals. We used public spectra for water (H2O), haemoglobin (HHb), oxy-haemoglobin (HbO2), eumelanin and pheomelanin, to create 1000 possible absorption combinations. These spectra simulations were used to understand the hypothetical limits, across a 450-800 nm wavelength range. These results have outlined the maximum oxy-haemoglobin concentrations that can be detected without interfering with eumelanin and pheomelanin. This initial and simple approach helped us to understand how eumelanin and pheomelanin absorption interferes and overlaps with low oxy-haemoglobin, which is a key biomarker for oxygen quantification in pulse oximeters and other non-invasive biomedical devices.

Novel technique utilizing polymethylmethacrylate cement for the treatment of pulsatile tinnitus caused by different sigmoid sinus pathologies.

PURPOSE: Sigmoid sinus anomalies such as dehiscence or diverticula may present with pulsatile tinnitus (PT) and low-frequency hearing loss. Occasionally, these symptoms are severe, necessitating resurfacing of the affected area to restore a normal-appearing sinus wall. This study describes three cases wherein we managed PT attributed to sigmoid sinus anomalies using polymethylmethacrylate (PMMA) bone cement, a novel material. METHODS: Three patients with PT without any history of illnesses initially underwent cortical mastoidectomy to expose the affected area and resurface the sinus wall. Subsequently, PMMA bone cement was used to reconstruct any bony defects causing PT symptoms. Viscosity of the bone cement was altered based on specific characteristics and causes of the affected area. Additionally, we performed the water occlusion test (WOT), audiological assessment, the Tinnitus Handicap Inventory score (THI), and temporal computed tomography, both pre- and postoperatively, to assess the extent of PT. RESULTS: Preoperatively, all three patients had tinnitus that dissipated with pressure on the neck and the water occlusion test (WOT), with no reported vertigo, trauma, or ear infections. Moreover, all three cases had a severe handicap according to the THI. In contrast, all cases had reduced PT and a significantly decreased THI score postoperatively, as well as no recurrence or complications and no instances of increased intracranial hypertension at the 12-month follow-up. CONCLUSION: All cases showed promising results, emphasizing the sustained benefits of this novel intervention for the management of PT.

What should otolaryngologists know about dural venous sinus stenting?

Dural venous sinus stenting is an emerging and exciting area in otolaryngology in collaboration with neurosurgeons and neuroradiologists. The first cases were reported 20 years ago. It is now considered part of the routine treatment of increased intracranial pressure due to transverse sinus stenosis. ENT doctors are the first to see these patients in their clinics, as sinus headaches, pulsating tinnitus, and dizziness are the most common symptoms. Previously, with limited success, high-dose diuretics and intracranial shunts had been the only options for treating these patients. Other methods, such as covering the sigmoid sinuses with graft material, appear to cause a sudden increase in intracranial pressure that can lead to blindness and even death. This overview summarizes the clinical and imaging characteristics of patients who will benefit from endovascular sinus stenting for elevated intracranial pressure.

Emotion Classification Based on Pulsatile Images Extracted from Short Facial Videos via Deep Learning.

Most human emotion recognition methods largely depend on classifying stereotypical facial expressions that represent emotions. However, such facial expressions do not necessarily correspond to actual emotional states and may correspond to communicative intentions. In other cases, emotions are hidden, cannot be expressed, or may have lower arousal manifested by less pronounced facial expressions, as may occur during passive video viewing. This study improves an emotion classification approach developed in a previous study, which classifies emotions remotely without relying on stereotypical facial expressions or contact-based methods, using short facial video data. In this approach, we desire to remotely sense transdermal cardiovascular spatiotemporal facial patterns associated with different emotional states and analyze this data via machine learning. In this paper, we propose several improvements, which include a better remote heart rate estimation via a preliminary skin segmentation, improvement of the heartbeat peaks and troughs detection process, and obtaining a better emotion classification accuracy by employing an appropriate deep learning classifier using an RGB camera input only with data. We used the dataset obtained in the previous study, which contains facial videos of 110 participants who passively viewed 150 short videos that elicited the following five emotion types: amusement, disgust, fear, sexual arousal, and no emotion, while three cameras with different wavelength sensitivities (visible spectrum, near-infrared, and longwave infrared) recorded them simultaneously. From the short facial videos, we extracted unique high-resolution spatiotemporal, physiologically affected features and examined them as input features with different deep-learning approaches. An EfficientNet-B0 model type was able to classify participants' emotional states with an overall average accuracy of 47.36% using a single input spatiotemporal feature map obtained from a regular RGB camera.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

[Effect and safety of pulsatile GnRH therapy for male congenital hypogonadotropic hypogonadism].

OBJECTIVE: To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congenital hypogonadotropic hypogonadism (CHH). METHODS: We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023. We treated the patients with gonadorelin at 7－15 µg, one pulse/90 min, and followed them up every month in the first 3 months and then every 3 to 6 months after treatment, for an average of 19.1±4.3 months, during which we recorded the height, body weight, penile length, testis volume, Tanner stages, levels of FSH, LH and T, semen parameters and adverse reactions of the patients, followed by comparison of the data obtained with the baseline. RESULTS: The levels of FSH, LH and T of the patients were dramatically elevated after treatment (P < 0.01). The T level of the 6 cases of cryptorchidism, however, failed to reach the normal value within 18.2 ± 8.6 months of follow-up. Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients, and spermatogenesis was observed in the semen in 33 cases (73.3%), with a mean sperm concentration of (18.2 ± 6.2) 106/ml, sperm progressive motility of (19.7 ± 6.5) %, and semen volume of (1.8 ± 0.6) ml. Eight of the cases achieved natural fertility, and another 3 achieved childbirth by assisted reproductive technology. As for adverse events, gynecomastia was observed in 8, subcutaneous induration in 6, and allergic reaction to therapeutic agent in 3 cases. CONCLUSION: Pulsatile GnRH therapy is an effective and safe strategy for male CHH. However, clinicians should choose appropriate approaches to different individual cases.

Peristaltic pumps adapted for laminar flow experiments enhance in vitro modeling of vascular cell behavior.

Endothelial cells (ECs) are the primary cellular constituent of blood vessels that are in direct contact with hemodynamic forces over their lifetime. Throughout the body, vessels experience different blood flow patterns and rates that alter vascular architecture and cellular behavior. Because of the complexities of studying blood flow in an intact organism, particularly during development, the field has increasingly relied on in vitro modeling of blood flow as a powerful technique for studying hemodynamic-dependent signaling mechanisms in ECs. While commercial flow systems that recirculate fluids exist, many commercially available pumps are peristaltic and best model pulsatile flow conditions. However, there are many important situations in which ECs experience laminar flow conditions in vivo, such as along long straight stretches of the vasculature. To understand EC function under these contexts, it is important to be able to reproducibly model laminar flow conditions in vitro. Here, we outline a method to reliably adapt commercially available peristaltic pumps to study laminar flow conditions. Our proof-of-concept study focuses on 2D models but could be further adapted to 3D environments to better model in vivo scenarios, such as organ development. Our studies make significant inroads into solving technical challenges associated with flow modeling and allow us to conduct functional studies toward understanding the mechanistic role of shear forces on vascular architecture, cellular behavior, and remodeling in diverse physiological contexts.

Pulsatile Basal Insulin Secretion Is Driven by Glycolytic Oscillations.

In fasted and fed states, blood insulin levels are oscillatory. While this phenomenon is well studied at high glucose levels, comparatively little is known about its origin under basal conditions. We propose a possible mechanism for basal insulin oscillations based on oscillations in glycolysis, demonstrated using an established mathematical model. At high glucose, this is superseded by a calcium-dependent mechanism.

Self-Boosting Vaccination Based on Pulsatile Antigen Release from Core-Shell Microparticles.

Vaccination is among the most effective ways to prevent infectious diseases. Subunit vaccines are safe but usually require multiple booster shots, which may lead to immunity loss and economic consume. In this study, a self-boosting vaccine is developed based on the pulsatile release of antigen from the core-shell microparticle after single-injection immunization. Self-healing technology applied to form an "antigen core" can avoid organic solvents from destroying the spatial structure of the antigen. The "antigen shell" is built-up by self-assemble of the antigen with the opposite charged polypeptide. Primary immunization occurs with the self-assembled film disintegration, and the booster comes with the microparticle degradation. The changing of antigen-specific antibodies after immunization with the core-shell microparticle vaccine is consistent with that caused by the two shots of immunization. The immune effect and safety evaluation results support the translational potential of this self-boosting core-shell microparticle vaccine.