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02/11/2025


The purpose of this study was to evaluate the efficacy of a new, single-dose bivalent vaccine containing porcine circovirus type 2b (PCV2b) and Mycoplasma hyopneumoniae against a dual PCV2b and M. hyopneumoniae challenge. At -25 days post challenge (dpc, 10 days of age), one pig group (designated as the vaccinated/challenged group) received a single, 1.0 ml dose of bivalent vaccine. Pigs in both the vaccinated/challenged and unvaccinated/challenged groups were then inoculated intranasally with PCV2b and M. hyopneumoniae at 0 dpc (35 days of age). Pigs in vaccinated/challenged group induced significantly higher levels of neutralizing antibodies against PCV2b and cell-mediated immunity against PCV2b and M. hyopneumonia when compared with pigs in unvaccinated/challenged group. The vaccination of pigs with a bivalent vaccine also reduced PCV2b viremia, reduced mycoplasmal nasal shedding, and decreased the severity of both lung and lymphoid lesions for PCV2b and M. hyopneumoniae infection, respectively. The results of this study demonstrated that the evaluated bivalent vaccine was effective in protecting pigs against PCV2b and M. hyopneumoniae infection.As lifestyle changes, the prevalence of diabetes increases every year. Diabetes-induced male reproductive dysfunction is predominantly due to increased oxidative stress and then results in sperm damage and infertility. Echinacea purpurea is a traditional medicinal herb and is well-known for its immune-modulatory, antioxidative, anti-inflammatory, anticancer, and antiviral activities. The Toll-like receptor 4 (TLR4) plays a critical role in innate immune responses leading to nuclear factor (NF)-κB phosphorylation and release of proinflammatory cytokines including nitric oxide (NO), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. However, the relation between Echinacea purpurea extract and TLR4 remains unclear. This study aimed to investigate the protective effects on male reproduction of Echinacea purpurea ethanol extract (EPE) against diabetic rats and whether the anti-inflammatory effects were through the TLR4 pathway. Diabetic male Sprague-Dawley (SD) rats were induced by streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). EPE was tested in three doses (93, 279, and 465 mg/kg p.o. daily) for 4 weeks. Besides, metformin administration (100 mg/kg/day) was treated as a positive control. Results indicated that EPE administration for about 4 weeks improved hyperglycemia and insulin resistance. Additionally, EPE increased sperm motility, protected sperm morphology and mitochondrial membrane potential, as well as protein for testosterone synthesis enzyme. In sperm superoxide dismutase, catalase, and glutathione antioxidants were increased, whereas proinflammatory cytokines, such as NO, IL-1β, and TNF-α were decreased. The testis protein content of TLR4 and downstream phospho-NF-κB p65 also were reduced. The EPE might reduce the production of proinflammatory cytokines via TLR4 pathways and improve diabetes-induced male infertility.Schistosomiasis, a major parasitic illness, has high morbidity and negative financial effects in subtropical and tropical countries, including Egypt. The present study investigated the therapeutic effects of Spirulina platensis (SP) and matcha green tea (MGT) in Schistosoma mansoni-infected mice combined with tracing their possible antioxidant and anti-inflammatory impacts and their protective potency. A total of 60 Swiss albino mice were randomly allocated into six groups (n = 10) control group (CNT, received normal saline); SP-MGT group [received oral SP (3 g/kg bodyweight/day) plus MGT (3 g/kg bodyweight/day)]; S. mansoni group (infected with S. mansoni cercariae, 100 ± 10/mouse, using the tail immersion method); SP-infected group (infected with S. mansoni and received oral SP); MGT-infected group (received oral MGT after S. mansoni infection); and SP-MGT-infected group (received combined treatment of SP and MGT after S. mansoni infection). Treatment with SP and MGT started 4 weeks after S. mansoni infectictive for S. mansoni infection. Liver and spleen tissue alterations were improved, the antioxidant systems were stimulated, and the inflammatory response was suppressed. Further research is recommended to investigate the mechanisms of the combined SP and MGT treatment effects to facilitate the development of novel therapies against this disease.Dairy goat animal welfare assessment protocols have been developed and conducted in Europe and the United Kingdom for dairy goats; however, there are no published reports of large-scale welfare assessment for dairy goats on farms in the Midwestern United States (US). Therefore, the objective of this study was to perform welfare assessment of lactating dairy goats and identify the most prevalent welfare issues on 30 farms across the Midwestern US. Thirty dairy goat farms (self-selected) were enrolled in the study if they shipped milk for human consumption (regardless of herd size). The number of lactating does on each farm ranged from 34 to 6,500 goats, with a median number of 158 lactating does (mean ± SD 602 ± 1,708 lactating does). The protocol used was developed from available literature on goat welfare assessment but modified for use in the Midwestern US. Observations were made without handling the animals and included 22 animal-based indicators evaluated at the group- and individual-level. The observations were conducted during ~3-5 h during a milking session (either morning or afternoon) and time in the home pen. Principal components analysis (PCA) was carried out on the welfare assessment data from each farm. The first two dimensions of the PCA explained 34.8% of the variation. https://www.selleckchem.com/products/og-l002.html The PCA biplot indicated correlations between indicators. The most prevalent conditions observed across the 30 farms included any knee calluses (80.9%), any claw overgrowth (51.4%), poor hygiene (14.9%), skin lesions (8.9%), poor hair coat condition (8.3%) and any ear pathology (8.0%). These results are the first to provide the Midwestern US dairy goat industry with information to improve commercial dairy goat welfare.Serum samples collected from 37 clinically normal bongo (Tragelaphus eurycerus) and 13 abnormal bongo were tested using assays for acute-phase proteins (APPs) and by protein electrophoresis. Abnormal bongo samples (n = 27) had significantly higher levels of fibrinogen (FIB) (p less then 0.001) and trending but not significantly increased haptoglobin (HP) (p = 0.07) vs. samples from normal bongo (n = 37). There were no significant differences in values for total white blood cell counts or for any of the fractions determined by protein electrophoresis. Clinically normal female bongo (n = 19) had significantly lower levels of FIB than normal males (n = 18) (p = 0.014), and this observation was also made with samples from the clinically abnormal group (p = 0.004). Many weak to moderate significant correlations were observed with increasing age, including increased globulins, FIB, and HP and decreased albumin-to-globulin (A/G) ratio and albumin. In clinical cases reviewed in this study, mild HP changes categorized this reactant as a minor APP, which contrasts with the major APP classification of HP in the related species of the cow.

02/11/2025


61). Radiological cup loosening was observed in 4 TM cups and 2 titanium cups (p = 1.0). At 6 years, the probability of not having radiological cup loosening was 97.4% (95% CI, 93.9-100) for the titanium cups and 95.1% for the TM cups (95% CI, 90.1-99.9) (p = 0.59). Another 5 cups were re-revised due to dislocation. Hips with a greater Paprosky defect showed a higher risk of loosening (p less then 0.05, hazard risk (HR) 3.04; 95% CI, 0.97-9.54). CONCLUSIONS This study shows there was no significant difference in re-revision due to aseptic loosening or radiological loosening between titanium and TM cups in revision surgery for acetabular bone loss. Both types of cups demonstrate excellent results with a low failure rate and minimal complications.Aim Recurrent implantation failure is an important issue in Assisted reproduction and despite various treatments that have been described before, there is no agreement on which is the best option.Methods This study was directed to assess the efficacy of autologous platelet-rich plasma (PRP) on pregnancy rate in recurrent implantation failure. Between 2016 and 2019, a total of 98 women who unsuccessful to be pregnant after three or more high-quality embryo transfers undergoing frozen-thawed embryo transfer with or without an intrauterine infusion of platelet-rich plasma. https://www.selleckchem.com/products/apcin.html Thus, 0.5 ml of platelet-rich plasma at 4-6 times higher concentration than peripheral blood infused intrauterine 48 h before embryo transfer. A control group underwent standard protocol.Results There were no significant differences between the two groups in terms of age, body mass index and duration and cause of infertility and total transferred embryos and kind of treatment protocol, but secondary infertility and endometrial thickness 96 h before embryo transfer, was more in the intervention group. The clinical pregnancy (48.3% versus 23.26; p = .001) and ongoing pregnancy (46.7% versus 11.7%; p = .001) and implantation rate (58.3% versus 25%; p = .001) was more significant in the intervention group rather than controls. In conclusion, intrauterine infusion of platelet-rich plasma 48 h before freeze-thawed embryo transfer may have more effectiveness in in vitro fertilization (IVF) outcomes in recurrent implantation failure.Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.OBJECTIVES To investigate the antidepressant effects of electroacupuncture (EA) on chronic unpredictable mild stress (CUMS) in rats, as well as the effects of EA on hippocampal neurons, synaptic morphology, and 5-hydroxytryptamine (HT) receptor expression. METHODS Forty adult male Wistar rats were randomly divided into normal control, CUMS, EA, and paroxetine groups. CUMS modeling was performed for 21 days, followed by 14 days of intervention rats in the EA group underwent stimulation of GV20 and GV29 acupuncture points for 30 minutes daily; rats in the paroxetine group were administered paroxetine daily. Behavioral tests, transmission electron microscopy, western blotting, and real-time quantitative polymerase chain reaction were used to evaluate the effects of the intervention. RESULTS EA treatment reversed the behavioral changes observed in rats due to CUMS modeling; it also improved the pathological changes in organelles and synaptic structures of hippocampal neurons, and upregulated the protein and mRNA expression levels of 5-HT1A receptor. There were no significant differences in 5-HT1B receptor protein and mRNA expression levels among the groups. CONCLUSIONS EA treatment can alleviate depression-like symptoms in CUMS rats. The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus.This is a report of a case with mucous membrane pemphigoid (MMP) with severe eye involvement and concurrent COVID-19 treated successfully using simultaneous high dose intravenous immunoglobulin (IVIg) and anti-viral treatment as hydroxychloroquine, lopinavir/ritonavir, and ribavirin. He had finished a 2-g cycle of rituximab (RTX) in late January. He was receiving mycophenolate mofetil (MMF) for one month and 30 mg prednisolone for three months until his hospitalization. Prednisolone was tapered to 15 mg when current COVID-19 was suspected, considering his recent cough, dyspnea, and fever.OBJECTIVE To investigate the value of ultrasound in the dynamic assessment of lung injury after acute paraquat poisoning. METHODS A prospective observational study was performed on patients with paraquat poisoning from admission to day 28 or discharge. Ultrasound assessment of the lungs was performtyed every 48 hours. The correlation of the lung ultrasound score (LUS) with other indicators was analyzed. RESULTS Twenty-six patients were enrolled, with an average age of 46 ± 16 years. The average toxic dose was 95 ± 51 mL. The intensive care unit (ICU) stay averaged 9 ± 8 days, and the 28-day mortality was 88.5%. There was a significant negative correlation between LUS and oxygenation index (rho = -0.896) and a significant positive correlation between LUS and carbon dioxide concentration (rho = 0.567). Lung ultrasound and computed tomography imaging correlated closely. CONCLUSION Lung ultrasound can reflect changes in lung status in patients with paraquat poisoning and can be used to evaluate lung injury in these patients.

02/10/2025


ystem to finish evaluating an entire testis section (computed with a PC (I7-6800k 4.0 GHzwith 32GB of RAM & 256G SSD) and a Titan 1080Ti GPU). Therefore, the CSS system is more accurate and faster compared to a human histologist in staging, and further optimization and development will not only lead to a complete staging of all 12 stages of mouse spermatogenesis but also could aid in the future diagnosis of human infertility. Moreover, the top-ranking histomorphological features identified by the CSS classifier are consistent with the primary features used by histologists in discriminating stages VI, VII-mVIII, and late VIII.Detecting early infarct (EI) plays an essential role in patient selection for reperfusion therapy in the management of acute ischemic stroke (AIS). EI volume at acute or hyper-acute stage can be measured using advanced pre-treatment imaging, such as MRI and CT perfusion. In this study, a novel multi-task learning approach, EIS-Net, is proposed to segment EI and score Alberta Stroke Program Early CT Score (ASPECTS) simultaneously on baseline non-contrast CT (NCCT) scans of AIS patients. The EIS-Net comprises of a 3D triplet convolutional neural network (T-CNN) for EI segmentation and a multi-region classification network for ASPECTS scoring. T-CNN has triple encoders with original NCCT, mirrored NCCT, and atlas as inputs, as well as one decoder. A comparison disparity block (CDB) is designed to extract and enhance image contexts. In the decoder, a multi-level attention gate module (MAGM) is developed to recalibrate the features of the decoder for both segmentation and classification tasks. Evaluations using a high-quality dataset comprising of baseline NCCT and concomitant diffusion weighted MRI (DWI) as reference standard of 260 patients with AIS show that the proposed EIS-Net can accurately segment EI. The EIS-Net segmented EI volume strongly correlates with EI volume on DWI (r=0.919), and the mean difference between the two volumes is 8.5 mL. For ASPECTS scoring, the proposed EIS-Net achieves an intraclass correlation coefficient of 0.78 for total 10-point ASPECTS and a kappa of 0.75 for dichotomized ASPECTS (≤ 4 vs. >4). Both EI segmentation and ASPECTS scoring tasks achieve state-of-the-art performances.Tumor classification and segmentation are two important tasks for computer-aided diagnosis (CAD) using 3D automated breast ultrasound (ABUS) images. However, they are challenging due to the significant shape variation of breast tumors and the fuzzy nature of ultrasound images (e.g., low contrast and signal to noise ratio). Considering the correlation between tumor classification and segmentation, we argue that learning these two tasks jointly is able to improve the outcomes of both tasks. In this paper, we propose a novel multi-task learning framework for joint segmentation and classification of tumors in ABUS images. The proposed framework consists of two sub-networks an encoder-decoder network for segmentation and a light-weight multi-scale network for classification. To account for the fuzzy boundaries of tumors in ABUS images, our framework uses an iterative training strategy to refine feature maps with the help of probability maps obtained from previous iterations. Experimental results based on a clinical dataset of 170 3D ABUS volumes collected from 107 patients indicate that the proposed multi-task framework improves tumor segmentation and classification over the single-task learning counterparts.Accurate liver tumor segmentation without contrast agents (non-enhanced images) avoids the contrast-agent-associated time-consuming and high risk, which offers radiologists quick and safe assistance to diagnose and treat the liver tumor. However, without contrast agents enhancing, the tumor in liver images presents low contrast and even invisible to naked eyes. Thus the liver tumor segmentation from non-enhanced images is quite challenging. We propose a Weakly-Supervised Teacher-Student network (WSTS) to address the liver tumor segmentation in non-enhanced images by leveraging additional box-level-labeled data (labeled with a tumor bounding-box). WSTS deploys a weakly-supervised teacher-student framework (TCH-ST), namely, a Teacher Module learns to detect and segment the tumor in enhanced images during training, which facilitates a Student Module to detect and segment the tumor in non-enhanced images independently during testing. To detect the tumor accurately, the WSTS proposes a Dual-strategy DRL (DDRL), which develops two tumor detection strategies by creatively introducing a relative-entropy bias in the DRL. To accurately predict a tumor mask for the box-level-labeled enhanced image and thus improve tumor segmentation in non-enhanced images, the WSTS proposes an Uncertainty-Sifting Self-Ensembling (USSE). The USSE exploits the weakly-labeled data with self-ensembling and evaluates the prediction reliability with a newly-designed Multi-scale Uncertainty-estimation. WSTS is validated with a 2D MRI dataset, where the experiment achieves 83.11% of Dice and 85.12% of Recall in 50 patient testing data after training by 200 patient data (half amount data is box-level-labeled). Such a great result illustrates the competence of WSTS to segment the liver tumor from non-enhanced images. Thus, WSTS has excellent potential to assist radiologists by liver tumor segmentation without contrast-agents.The main goal of this work is to improve the quality of simultaneous multi-slice (SMS) reconstruction for diffusion MRI. We accomplish this by developing an image domain method that reaps the benefits of both SENSE and GRAPPA-type approaches and enables image regularization in an optimization framework. We propose a new approach termed regularized image domain split slice-GRAPPA (RI-SSG), which establishes an optimization framework for SMS reconstruction. Within this framework, we use a robust forward model to take advantage of both the SENSE model with explicit sensitivity estimations and the SSG model with implicit kernel relationship among coil images. The proposed approach also allows combining of coil images to increase the SNR and enables image domain regularization on estimated coil-combined single slices. https://www.selleckchem.com/JAK.html We compare the performance of RI-SSG with that of SENSE and SSG using in-vivo diffusion EPI datasets with simulated and actual SMS acquisitions collected on a 3T MR scanner. Reconstructed diffusion-weighted images (DWIs) and the resulting diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) maps are analyzed to evaluate the quantitative and qualitative performance of the three methods.

Videos

No, the vitamin K shots that are supposed to be great for newborns do not contain high amounts of aluminum like you may have heard.

But they do contain something else, says scientist Marcella Piper-Terry.

In 2016 the American College of Pediatricians made a public statement expressing concern that the amount of Polysorbate 80 in Gardasil HPV vaccines was linked to the development of premature menopause in young women.

As a side note, Polysorbate 80 is also often used to induce INFERTILITY in lab rats.

Now … guess what contains 200x the amount of Polysorbate 80 as Gardasil?

Vitamin K shots.

FULL INTERVIEW: https://live.childrenshealthdefense.org/chd-tv/shows/good-morning-chd/dangers-of-vitamin-k-shot--free-speech-violation/

Could the many carcinogenic chemicals in microplastics be linked to a plethora of health issues, including autism + infertility?

Watch the FULL U.S. Senate Committee on Environment + Public Works Hearing on #CHDTV ?

https://live.childrenshealthdefense.org/chd-tv/events/understanding-the-presence-of-microplastics-in-water-or-feb-27/understanding-presence-microplastics-water-feb-27/

09/17/2023

The latest study on infertility released by the World Health Organization says 1 in 6 individuals globally are affected by infertility in their lifetime. On this edition of 360 View, Scottie Nell Hughes speaks with Professor Marcia Inhorn of Yale University about the reasons why infertility in some regions of the world is growing while other regions are on the decline.

People

Sorry, no results were found.

Videos

No, the vitamin K shots that are supposed to be great for newborns do not contain high amounts of aluminum like you may have heard.

But they do contain something else, says scientist Marcella Piper-Terry.

In 2016 the American College of Pediatricians made a public statement expressing concern that the amount of Polysorbate 80 in Gardasil HPV vaccines was linked to the development of premature menopause in young women.

As a side note, Polysorbate 80 is also often used to induce INFERTILITY in lab rats.

Now … guess what contains 200x the amount of Polysorbate 80 as Gardasil?

Vitamin K shots.

FULL INTERVIEW: https://live.childrenshealthdefense.org/chd-tv/shows/good-morning-chd/dangers-of-vitamin-k-shot--free-speech-violation/

Could the many carcinogenic chemicals in microplastics be linked to a plethora of health issues, including autism + infertility?

Watch the FULL U.S. Senate Committee on Environment + Public Works Hearing on #CHDTV ?

https://live.childrenshealthdefense.org/chd-tv/events/understanding-the-presence-of-microplastics-in-water-or-feb-27/understanding-presence-microplastics-water-feb-27/

09/17/2023

The latest study on infertility released by the World Health Organization says 1 in 6 individuals globally are affected by infertility in their lifetime. On this edition of 360 View, Scottie Nell Hughes speaks with Professor Marcia Inhorn of Yale University about the reasons why infertility in some regions of the world is growing while other regions are on the decline.

On this episode of The Cost of Everything we take a closer look at the surprising cost of global infertility. While many so-called experts complain about overpopulation, more and more countries are falling below replacement fertility rates. Host Christy Ai discusses the high costs of fertility aids like surrogacy and IVF cycles as well as which countries are suffering the most with fertility issues with co-founder of BabyQuest Pamela Hirsch.

CHD volunteers enjoy sharing info about our latest docu-film: “Infertility: A Diabolical Agenda,” specifically to the African-American community in Brooklyn b/c they are "more open to this information" as they are largely “anti-mandate.”

Learn More :syringe: www.InfertilityMovie.org

#CHDTV

Posts

02/11/2025


The purpose of this study was to evaluate the efficacy of a new, single-dose bivalent vaccine containing porcine circovirus type 2b (PCV2b) and Mycoplasma hyopneumoniae against a dual PCV2b and M. hyopneumoniae challenge. At -25 days post challenge (dpc, 10 days of age), one pig group (designated as the vaccinated/challenged group) received a single, 1.0 ml dose of bivalent vaccine. Pigs in both the vaccinated/challenged and unvaccinated/challenged groups were then inoculated intranasally with PCV2b and M. hyopneumoniae at 0 dpc (35 days of age). Pigs in vaccinated/challenged group induced significantly higher levels of neutralizing antibodies against PCV2b and cell-mediated immunity against PCV2b and M. hyopneumonia when compared with pigs in unvaccinated/challenged group. The vaccination of pigs with a bivalent vaccine also reduced PCV2b viremia, reduced mycoplasmal nasal shedding, and decreased the severity of both lung and lymphoid lesions for PCV2b and M. hyopneumoniae infection, respectively. The results of this study demonstrated that the evaluated bivalent vaccine was effective in protecting pigs against PCV2b and M. hyopneumoniae infection.As lifestyle changes, the prevalence of diabetes increases every year. Diabetes-induced male reproductive dysfunction is predominantly due to increased oxidative stress and then results in sperm damage and infertility. Echinacea purpurea is a traditional medicinal herb and is well-known for its immune-modulatory, antioxidative, anti-inflammatory, anticancer, and antiviral activities. The Toll-like receptor 4 (TLR4) plays a critical role in innate immune responses leading to nuclear factor (NF)-κB phosphorylation and release of proinflammatory cytokines including nitric oxide (NO), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. However, the relation between Echinacea purpurea extract and TLR4 remains unclear. This study aimed to investigate the protective effects on male reproduction of Echinacea purpurea ethanol extract (EPE) against diabetic rats and whether the anti-inflammatory effects were through the TLR4 pathway. Diabetic male Sprague-Dawley (SD) rats were induced by streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). EPE was tested in three doses (93, 279, and 465 mg/kg p.o. daily) for 4 weeks. Besides, metformin administration (100 mg/kg/day) was treated as a positive control. Results indicated that EPE administration for about 4 weeks improved hyperglycemia and insulin resistance. Additionally, EPE increased sperm motility, protected sperm morphology and mitochondrial membrane potential, as well as protein for testosterone synthesis enzyme. In sperm superoxide dismutase, catalase, and glutathione antioxidants were increased, whereas proinflammatory cytokines, such as NO, IL-1β, and TNF-α were decreased. The testis protein content of TLR4 and downstream phospho-NF-κB p65 also were reduced. The EPE might reduce the production of proinflammatory cytokines via TLR4 pathways and improve diabetes-induced male infertility.Schistosomiasis, a major parasitic illness, has high morbidity and negative financial effects in subtropical and tropical countries, including Egypt. The present study investigated the therapeutic effects of Spirulina platensis (SP) and matcha green tea (MGT) in Schistosoma mansoni-infected mice combined with tracing their possible antioxidant and anti-inflammatory impacts and their protective potency. A total of 60 Swiss albino mice were randomly allocated into six groups (n = 10) control group (CNT, received normal saline); SP-MGT group [received oral SP (3 g/kg bodyweight/day) plus MGT (3 g/kg bodyweight/day)]; S. mansoni group (infected with S. mansoni cercariae, 100 ± 10/mouse, using the tail immersion method); SP-infected group (infected with S. mansoni and received oral SP); MGT-infected group (received oral MGT after S. mansoni infection); and SP-MGT-infected group (received combined treatment of SP and MGT after S. mansoni infection). Treatment with SP and MGT started 4 weeks after S. mansoni infectictive for S. mansoni infection. Liver and spleen tissue alterations were improved, the antioxidant systems were stimulated, and the inflammatory response was suppressed. Further research is recommended to investigate the mechanisms of the combined SP and MGT treatment effects to facilitate the development of novel therapies against this disease.Dairy goat animal welfare assessment protocols have been developed and conducted in Europe and the United Kingdom for dairy goats; however, there are no published reports of large-scale welfare assessment for dairy goats on farms in the Midwestern United States (US). Therefore, the objective of this study was to perform welfare assessment of lactating dairy goats and identify the most prevalent welfare issues on 30 farms across the Midwestern US. Thirty dairy goat farms (self-selected) were enrolled in the study if they shipped milk for human consumption (regardless of herd size). The number of lactating does on each farm ranged from 34 to 6,500 goats, with a median number of 158 lactating does (mean ± SD 602 ± 1,708 lactating does). The protocol used was developed from available literature on goat welfare assessment but modified for use in the Midwestern US. Observations were made without handling the animals and included 22 animal-based indicators evaluated at the group- and individual-level. The observations were conducted during ~3-5 h during a milking session (either morning or afternoon) and time in the home pen. Principal components analysis (PCA) was carried out on the welfare assessment data from each farm. The first two dimensions of the PCA explained 34.8% of the variation. https://www.selleckchem.com/products/og-l002.html The PCA biplot indicated correlations between indicators. The most prevalent conditions observed across the 30 farms included any knee calluses (80.9%), any claw overgrowth (51.4%), poor hygiene (14.9%), skin lesions (8.9%), poor hair coat condition (8.3%) and any ear pathology (8.0%). These results are the first to provide the Midwestern US dairy goat industry with information to improve commercial dairy goat welfare.Serum samples collected from 37 clinically normal bongo (Tragelaphus eurycerus) and 13 abnormal bongo were tested using assays for acute-phase proteins (APPs) and by protein electrophoresis. Abnormal bongo samples (n = 27) had significantly higher levels of fibrinogen (FIB) (p less then 0.001) and trending but not significantly increased haptoglobin (HP) (p = 0.07) vs. samples from normal bongo (n = 37). There were no significant differences in values for total white blood cell counts or for any of the fractions determined by protein electrophoresis. Clinically normal female bongo (n = 19) had significantly lower levels of FIB than normal males (n = 18) (p = 0.014), and this observation was also made with samples from the clinically abnormal group (p = 0.004). Many weak to moderate significant correlations were observed with increasing age, including increased globulins, FIB, and HP and decreased albumin-to-globulin (A/G) ratio and albumin. In clinical cases reviewed in this study, mild HP changes categorized this reactant as a minor APP, which contrasts with the major APP classification of HP in the related species of the cow.

02/11/2025


61). Radiological cup loosening was observed in 4 TM cups and 2 titanium cups (p = 1.0). At 6 years, the probability of not having radiological cup loosening was 97.4% (95% CI, 93.9-100) for the titanium cups and 95.1% for the TM cups (95% CI, 90.1-99.9) (p = 0.59). Another 5 cups were re-revised due to dislocation. Hips with a greater Paprosky defect showed a higher risk of loosening (p less then 0.05, hazard risk (HR) 3.04; 95% CI, 0.97-9.54). CONCLUSIONS This study shows there was no significant difference in re-revision due to aseptic loosening or radiological loosening between titanium and TM cups in revision surgery for acetabular bone loss. Both types of cups demonstrate excellent results with a low failure rate and minimal complications.Aim Recurrent implantation failure is an important issue in Assisted reproduction and despite various treatments that have been described before, there is no agreement on which is the best option.Methods This study was directed to assess the efficacy of autologous platelet-rich plasma (PRP) on pregnancy rate in recurrent implantation failure. Between 2016 and 2019, a total of 98 women who unsuccessful to be pregnant after three or more high-quality embryo transfers undergoing frozen-thawed embryo transfer with or without an intrauterine infusion of platelet-rich plasma. https://www.selleckchem.com/products/apcin.html Thus, 0.5 ml of platelet-rich plasma at 4-6 times higher concentration than peripheral blood infused intrauterine 48 h before embryo transfer. A control group underwent standard protocol.Results There were no significant differences between the two groups in terms of age, body mass index and duration and cause of infertility and total transferred embryos and kind of treatment protocol, but secondary infertility and endometrial thickness 96 h before embryo transfer, was more in the intervention group. The clinical pregnancy (48.3% versus 23.26; p = .001) and ongoing pregnancy (46.7% versus 11.7%; p = .001) and implantation rate (58.3% versus 25%; p = .001) was more significant in the intervention group rather than controls. In conclusion, intrauterine infusion of platelet-rich plasma 48 h before freeze-thawed embryo transfer may have more effectiveness in in vitro fertilization (IVF) outcomes in recurrent implantation failure.Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.OBJECTIVES To investigate the antidepressant effects of electroacupuncture (EA) on chronic unpredictable mild stress (CUMS) in rats, as well as the effects of EA on hippocampal neurons, synaptic morphology, and 5-hydroxytryptamine (HT) receptor expression. METHODS Forty adult male Wistar rats were randomly divided into normal control, CUMS, EA, and paroxetine groups. CUMS modeling was performed for 21 days, followed by 14 days of intervention rats in the EA group underwent stimulation of GV20 and GV29 acupuncture points for 30 minutes daily; rats in the paroxetine group were administered paroxetine daily. Behavioral tests, transmission electron microscopy, western blotting, and real-time quantitative polymerase chain reaction were used to evaluate the effects of the intervention. RESULTS EA treatment reversed the behavioral changes observed in rats due to CUMS modeling; it also improved the pathological changes in organelles and synaptic structures of hippocampal neurons, and upregulated the protein and mRNA expression levels of 5-HT1A receptor. There were no significant differences in 5-HT1B receptor protein and mRNA expression levels among the groups. CONCLUSIONS EA treatment can alleviate depression-like symptoms in CUMS rats. The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus.This is a report of a case with mucous membrane pemphigoid (MMP) with severe eye involvement and concurrent COVID-19 treated successfully using simultaneous high dose intravenous immunoglobulin (IVIg) and anti-viral treatment as hydroxychloroquine, lopinavir/ritonavir, and ribavirin. He had finished a 2-g cycle of rituximab (RTX) in late January. He was receiving mycophenolate mofetil (MMF) for one month and 30 mg prednisolone for three months until his hospitalization. Prednisolone was tapered to 15 mg when current COVID-19 was suspected, considering his recent cough, dyspnea, and fever.OBJECTIVE To investigate the value of ultrasound in the dynamic assessment of lung injury after acute paraquat poisoning. METHODS A prospective observational study was performed on patients with paraquat poisoning from admission to day 28 or discharge. Ultrasound assessment of the lungs was performtyed every 48 hours. The correlation of the lung ultrasound score (LUS) with other indicators was analyzed. RESULTS Twenty-six patients were enrolled, with an average age of 46 ± 16 years. The average toxic dose was 95 ± 51 mL. The intensive care unit (ICU) stay averaged 9 ± 8 days, and the 28-day mortality was 88.5%. There was a significant negative correlation between LUS and oxygenation index (rho = -0.896) and a significant positive correlation between LUS and carbon dioxide concentration (rho = 0.567). Lung ultrasound and computed tomography imaging correlated closely. CONCLUSION Lung ultrasound can reflect changes in lung status in patients with paraquat poisoning and can be used to evaluate lung injury in these patients.

02/10/2025


ystem to finish evaluating an entire testis section (computed with a PC (I7-6800k 4.0 GHzwith 32GB of RAM & 256G SSD) and a Titan 1080Ti GPU). Therefore, the CSS system is more accurate and faster compared to a human histologist in staging, and further optimization and development will not only lead to a complete staging of all 12 stages of mouse spermatogenesis but also could aid in the future diagnosis of human infertility. Moreover, the top-ranking histomorphological features identified by the CSS classifier are consistent with the primary features used by histologists in discriminating stages VI, VII-mVIII, and late VIII.Detecting early infarct (EI) plays an essential role in patient selection for reperfusion therapy in the management of acute ischemic stroke (AIS). EI volume at acute or hyper-acute stage can be measured using advanced pre-treatment imaging, such as MRI and CT perfusion. In this study, a novel multi-task learning approach, EIS-Net, is proposed to segment EI and score Alberta Stroke Program Early CT Score (ASPECTS) simultaneously on baseline non-contrast CT (NCCT) scans of AIS patients. The EIS-Net comprises of a 3D triplet convolutional neural network (T-CNN) for EI segmentation and a multi-region classification network for ASPECTS scoring. T-CNN has triple encoders with original NCCT, mirrored NCCT, and atlas as inputs, as well as one decoder. A comparison disparity block (CDB) is designed to extract and enhance image contexts. In the decoder, a multi-level attention gate module (MAGM) is developed to recalibrate the features of the decoder for both segmentation and classification tasks. Evaluations using a high-quality dataset comprising of baseline NCCT and concomitant diffusion weighted MRI (DWI) as reference standard of 260 patients with AIS show that the proposed EIS-Net can accurately segment EI. The EIS-Net segmented EI volume strongly correlates with EI volume on DWI (r=0.919), and the mean difference between the two volumes is 8.5 mL. For ASPECTS scoring, the proposed EIS-Net achieves an intraclass correlation coefficient of 0.78 for total 10-point ASPECTS and a kappa of 0.75 for dichotomized ASPECTS (≤ 4 vs. >4). Both EI segmentation and ASPECTS scoring tasks achieve state-of-the-art performances.Tumor classification and segmentation are two important tasks for computer-aided diagnosis (CAD) using 3D automated breast ultrasound (ABUS) images. However, they are challenging due to the significant shape variation of breast tumors and the fuzzy nature of ultrasound images (e.g., low contrast and signal to noise ratio). Considering the correlation between tumor classification and segmentation, we argue that learning these two tasks jointly is able to improve the outcomes of both tasks. In this paper, we propose a novel multi-task learning framework for joint segmentation and classification of tumors in ABUS images. The proposed framework consists of two sub-networks an encoder-decoder network for segmentation and a light-weight multi-scale network for classification. To account for the fuzzy boundaries of tumors in ABUS images, our framework uses an iterative training strategy to refine feature maps with the help of probability maps obtained from previous iterations. Experimental results based on a clinical dataset of 170 3D ABUS volumes collected from 107 patients indicate that the proposed multi-task framework improves tumor segmentation and classification over the single-task learning counterparts.Accurate liver tumor segmentation without contrast agents (non-enhanced images) avoids the contrast-agent-associated time-consuming and high risk, which offers radiologists quick and safe assistance to diagnose and treat the liver tumor. However, without contrast agents enhancing, the tumor in liver images presents low contrast and even invisible to naked eyes. Thus the liver tumor segmentation from non-enhanced images is quite challenging. We propose a Weakly-Supervised Teacher-Student network (WSTS) to address the liver tumor segmentation in non-enhanced images by leveraging additional box-level-labeled data (labeled with a tumor bounding-box). WSTS deploys a weakly-supervised teacher-student framework (TCH-ST), namely, a Teacher Module learns to detect and segment the tumor in enhanced images during training, which facilitates a Student Module to detect and segment the tumor in non-enhanced images independently during testing. To detect the tumor accurately, the WSTS proposes a Dual-strategy DRL (DDRL), which develops two tumor detection strategies by creatively introducing a relative-entropy bias in the DRL. To accurately predict a tumor mask for the box-level-labeled enhanced image and thus improve tumor segmentation in non-enhanced images, the WSTS proposes an Uncertainty-Sifting Self-Ensembling (USSE). The USSE exploits the weakly-labeled data with self-ensembling and evaluates the prediction reliability with a newly-designed Multi-scale Uncertainty-estimation. WSTS is validated with a 2D MRI dataset, where the experiment achieves 83.11% of Dice and 85.12% of Recall in 50 patient testing data after training by 200 patient data (half amount data is box-level-labeled). Such a great result illustrates the competence of WSTS to segment the liver tumor from non-enhanced images. Thus, WSTS has excellent potential to assist radiologists by liver tumor segmentation without contrast-agents.The main goal of this work is to improve the quality of simultaneous multi-slice (SMS) reconstruction for diffusion MRI. We accomplish this by developing an image domain method that reaps the benefits of both SENSE and GRAPPA-type approaches and enables image regularization in an optimization framework. We propose a new approach termed regularized image domain split slice-GRAPPA (RI-SSG), which establishes an optimization framework for SMS reconstruction. Within this framework, we use a robust forward model to take advantage of both the SENSE model with explicit sensitivity estimations and the SSG model with implicit kernel relationship among coil images. The proposed approach also allows combining of coil images to increase the SNR and enables image domain regularization on estimated coil-combined single slices. https://www.selleckchem.com/JAK.html We compare the performance of RI-SSG with that of SENSE and SSG using in-vivo diffusion EPI datasets with simulated and actual SMS acquisitions collected on a 3T MR scanner. Reconstructed diffusion-weighted images (DWIs) and the resulting diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) maps are analyzed to evaluate the quantitative and qualitative performance of the three methods.

02/09/2025


In this review, 170 natural substances, including steroid, diterpenoid, sesquiterpenoid, peptide, prostaglandin, base, chlorolipid, bicyclolactone, amide, piperazine, polyketide, glycerol, benzoic acid, glycyrrhetyl amino acid, hexitol, pentanoic acid, aminoethyl ester, octadecanone, alkaloid, and a 53-kD allergenic component from octocorals belonging to genus Dendronephthya, were listed. Some of these compounds displayed potential bioactivities.There is a pressing demand to improve the performance of cost-effective soft magnetic materials for use in high performance sensors and devices. Giant Magneto-impedance effect (GMI), or fast single domain wall (DW) propagation can be observed in properly processed magnetic microwires. In this paper we have identified the routes to obtain microwires with unique combination of magnetic properties allowing observation of fast and single DW propagation and GMI effect in the same microwire. By modifying the annealing conditions, we have found the appropriate regimes allowing achievement of the highest GMI ratio and the fastest DW dynamics. The observed experimental results are discussed considering the radial distribution of magnetic anisotropy and the correlation of GMI effect, and DW dynamics with bulk and surface magnetization processes. Studies of both Fe- and Co-rich microwires, using the magneto-optical Kerr effect, MOKE, provide information on the magnetic structure in the outer shell of microwires. We have demonstrated the existence of the spiral helical structure in both studied microwires. At the same time, torsion mechanical stresses induce helical bistability in the same microwires, which allow us to consider these microwires as materials suitable for sensors based on the large Barkhausen jump.Clean energy technologies represent a hot topic for research communities worldwide. Hydrogen fuel, a prized alternative to fossil fuels, displays weaknesses such as the poisoning by impurities of the precious metal catalyst which controls the reaction involved in its production. Thus, separating H2 out of the other gases, meaning CH4, CO, CO2, N2, and H2O is essential. We present a rotating partially double-walled carbon nanotube membrane design for hydrogen separation and evaluate its performance using molecular dynamics simulations by imposing three discrete angular velocities. We provide a nano-perspective of the gas behaviors inside the membrane and extract key insights from the filtration process, pore placement, flux, and permeance of the membrane. We display a very high selectivity case (ω = 180° ps-1) and show that the outcome of Molecular Dynamics (MD) simulations can be both intuitive and counter-intuitive when increasing the ω parameter (ω = 270° ps-1; ω = 360° ps-1). Thus, in the highly selective, ω = 180° ps-1, only H2 molecules and 1-2 H2O molecules pass into the filtrate area. In the ω = 270° ps-1, H2, CO, CH4, N2, and H2O molecules were observed to pass, while, perhaps counter-intuitively, in the third case, with the highest imposed angular velocity of 360° ps-1 only CH4 and H2 molecules were able to pass through the pores leading to the filtrate area.Current therapeutic medicines for endometriosis cannot be administered during assisted reproductive technology (ART) because they have bad effects during pregnancy. In this study, we created an animal model of endometriosis and evaluated the therapeutic effect of progestin (Dienogest), dopamine agonist (Cabergoline), and their combination (Dienogest + Cabergoline). We established a mouse model mimicking human endometriosis. The mice with endometriosis were then treated with a single drug (Dienogest or Cabergoline) or both drugs (Dienogest + Cabergoline) for 14 days. An immunohistological study was then performed to analyze inflammatory lesions in the recipient mice. Real-time polymerase chain reaction (RT-PCR) and Western blotting were also performed to determine the levels of genes and proteins in inflammatory lesions to assess the recovery of endometriosis. https://www.selleckchem.com/products/nivolumab.html Histologic staining showed that all medication groups showed a clear decrease in the inflammatory phenotype in the uterus, peritoneum, and intestine. Gene and protein expression analysis showed a therapeutic effect in all medication groups. In conclusion, Cabergoline had a therapeutic effect similar to that of Dienogest and could be used as an alternative to Dienogest during ART for patients with infertility; compared to the individual drugs, the combination treatment has a synergistic effect on endometriosis.Research on workaholism (also called work addiction by some scholars, especially in the clinical psychology field) has increased substantially in the last few years [...].There is a wide consensus in considering Africa as the birthplace of anatomically modern humans (AMH), but the dispersal pattern and the main routes followed by our ancestors to colonize the world are still matters of debate. It is still an open question whether AMH left Africa through a single process, dispersing almost simultaneously over Asia and Europe, or in two main waves, first through the Arab Peninsula into southern Asia and Australo-Melanesia, and later through a northern route crossing the Levant. The development of new methodologies for inferring population history and the availability of worldwide high-coverage whole-genome sequences did not resolve this debate. In this work, we test the two main out-of-Africa hypotheses through an Approximate Bayesian Computation approach, based on the Random-Forest algorithm. We evaluated the ability of the method to discriminate between the alternative models of AMH out-of-Africa, using simulated data. Once assessed that the models are distinguishable, we compared simulated data with real genomic variation, from modern and archaic populations. This analysis showed that a model of multiple dispersals is four-fold as likely as the alternative single-dispersal model. According to our estimates, the two dispersal processes may be placed, respectively, around 74,000 and around 46,000 years ago.The cuticle, a protective cuticular barrier present in almost all primary aerial plant organs, has a composition that varies between plant species. As a part of the apple peel, cuticle and epicuticular waxes have an important role in the skin appearance and quality characteristic in fresh fruits destined for human consumption. The specific composition and structural characteristics of cutin from two apple varieties, "golden delicious" and "red delicious", were obtained by enzymatic protocols and studied by means of cross polarization magic angle spinning nuclear magnetic resonance (CP-MAS 13C NMR), attenuated total reflection infrared spectroscopy (ATR-FTIR), and mass spectrometry, and were morphologically characterized by specialized microscopy techniques (atomic force microscopy (AFM), confocal laser scanning microscopy (CLMS), and scanning electron microscopy (SEM)). According to CP-MAS 13C NMR and ATR-FTIR analysis, cutins from both varieties are mainly composed of aliphatics and a small difference is shown between them.

02/08/2025


Approximately a century after D'Arcy Thompson's On Growth and Form, there continues to be widespread interest in the biophysical and mathematical basis of morphogenesis. Particularly over the past 20 years, this interest has led to great advances in our understanding of a broad range of processes in embryonic development through a quantitative, mechanically driven framework. Nowhere in vertebrate development is this more apparent than the development of endodermally derived organs. Here, we discuss recent advances in the study of gut development that have emerged primarily from mechanobiology-motivated approaches that span from gut tube morphogenesis and later organogenesis of the respiratory and gastrointestinal systems.Since its introduction to clinical practice, preimplantation genetic testing (PGT) has become a standard of care for couples at risk of having children with monogenic disease, and for chromosomal aneuploidy to improve outcomes for patients with infertility. The primary objective of PGT is to reduce the risk of miscarriage and genetic disease and to improve the success of infertility treatment with the delivery of a healthy child. Until recently, the application of PGT to more common but complex polygenic disease was not possible, as the genetic contribution to polygenic disease has been difficult to determine, and the concept of embryo selection across multiple genetic loci has been difficult to comprehend. Several achievements, including the ability to obtain accurate, genome-wide genotypes of the human embryo, and the development of population level biobanks have now made PGT for polygenic disease risk applicable in clinical practice. With the rapid advances in embryonic polygenic risk scoring, diverse considerations beyond technical capability have been introduced.Phytochemicals in fruits and vegetables produce health benefits, but questions remain regarding their bioavailability, molecular targets, and mechanism of action. Here, we address these issues by considering the prebiotic and biological properties of phytochemicals. A fraction of phytochemicals consumed orally passes through the gut lumen, where it modulates the composition of the gut microbiota and maintains intestinal integrity. Phytochemicals and microbiota-derived metabolites that are absorbed by the organism comprise compounds that, at low doses, induce stress resistance mechanisms, including autophagy, DNA repair, and expression of detoxifying and antioxidant enzymes. We propose that these mechanisms improve cellular and organ function and can account for the promiscuous bioactivities of phytochemicals, despite their limited bioavailability and extremely varied chemical structures.Cutaneous squamous cell carcinoma (cSCC) and melanoma encompass the majority of all malignant skin cancers. There has been an increase in their incidence globally in recent decades. In cases of high-risk, unresectable, or metastatic disease; or when patient factors or preferences limit the availability of conventional surgery or radiotherapy; or a systemic therapy is often warranted. Our improved understanding of the molecular and immune pathogenesis underlying tumor growth and development has been critical in advancing cancer therapeutics. Over the past several years, several new systemic agents have been approved for both diseases. The role of cytotoxic chemotherapy is gradually waning with the introduction of targeted therapy and immunotherapy. In this article, we review the current and relevant literature and evidence of cytotoxic chemotherapy, targeted therapy, and immune checkpoint inhibitors in the adjuvant and neoadjuvant settings for cSCC and melanoma. Additionally, we describe their role in the unresectable or metastatic disease setting.Pulmonary arterial hypertension remains a progressive, life-limiting disease despite optimal medical therapy. https://www.selleckchem.com/products/bay-985.html Pulmonary artery denervation has arisen as a novel intervention in the treatment of pulmonary arterial hypertension, and other forms of pulmonary hypertension, with the aim of reducing the sympathetic activity of the pulmonary circulation. Pre-clinical studies and initial clinical trials have demonstrated that the technique can be performed safely with some positive effects on clinical, haemodynamic and echocardiographic markers of disease. The scope of the technique in current practice remains limited given the absence of well-designed, large-scale, international randomised controlled clinical trials. This review provides an overview of this exciting new treatment modality, including pathophysiology, technical innovations and recent trial results.Measles virus, a member of the genus Morbillivirus, is highly contagious and still shows considerable mortality with over 100000 deaths annually, although efficient attenuated vaccines exist. Recent studies of measles virus haemagglutinin (MeV-H) and its receptor, including crystallographic and electron microscopic structural analyses combined with functional assays, have revealed how the MeV-H protein recognizes its cognate receptors, SLAM and Nectin-4, and how the glycan shield ensures effective vaccination. In addition, the crystal structure of the MeV-F protein indicated its similarity to those of other paramyxoviruses. Taking into account these data, several models of viral entry/membrane fusion of measles viruses and related paramyxoviruses have been proposed. Furthermore, anti-MeV-F inhibitors targeted to specific regions to inhibit MeV-F protein activation were reported, with potency for preventing MeV infection. The inhibitors targeted for entry events may potentially be applied to treatment of MeV-derived diseases, although escape mutations and drug profiles should be considered.There have been several significant advances in cancer treatment in the last decade that are applicable to the treatment of melanoma and advanced nonmelanoma skin cancers. Among these are the development of immune checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death legand-1 (PDL-1) axis, as well as targeted inhibitors of the BRAF/MEK signaling cascade in melanoma, and the hedgehog signaling pathway in basal cell carcinoma (BCC). These immune-based and targeted therapies have dramatically changed the treatment options for locally advanced and metastatic melanoma, Merkel's cell carcinoma, cutaneous squamous cell carcinoma (cSCC), and BCC. In this article, we will briefly review the currently approved targeted and immunotherapy-based treatments for locally advanced and metastatic melanoma, Merkel's cell carcinoma, and cSCC and discuss various combinations of approved therapies, as well as emerging therapeutic candidates that are currently in clinical trials, including novel checkpoint inhibitors in development, intratumoral oncolytic agents (viral and nonviral), and various immune-based therapies such as toll-like receptor (TLR) agonists, adoptive T-cell therapy, T-cell costimulation, and innate immune cell therapy.