Non-treated Group Research Articles

Research on the influence of yogalates comprehensive rehabilitation training on postoperative recovery of breast cancer patients

BackgroundIn the present study, we analyzed the effects of comprehensive yogalates rehabilitation training on side effects caused by postoperative adjuvant treatment and postoperative physical and mental health in breast cancer patients who had undergone radical mastectomy.The purpose of this investigation was to test the hypothesis that 12 weeks of yogalates training would reduce the peripheral diameter of the upper arm, improve flexibility and posture, and improve sleep quality compared with a non-treated control group. Methods36 women with breast cancer who had undergone radical mastectomy in Shanghai were selected and randomly divided into the experimental group (n=20) and the control group (n=16). The patients in the experimental group underwent yogalates comprehensive rehabilitation training, while the control group did not participate in yogalates course. Anthropometric measurements and the "Pittsburgh Sleep Quality Index (PSQI)" questionnaire were administered to both the experimental and control groups before and after the training sessions. ResultsThe experimental group corrected the hunchback posture through yogalates training. Spine extension increased their height and decreased their BMI. The range of motion of upper arm joints in extension, bending and abduction increased. The peripheral diameter of the upper arm decreased, the grip strength increased, and the sleep quality gradually improved. Conclusion(1)Prolonging the period of yogalates training stabilized and improve the physical and mental health of patients. (2)In yogalates course, providing proper guidance to patients for diaphragmatic breathing and incorporating yoga relaxation techniques can effectively enhance the sleep quality of patients.(3)Exercise regimens must be designed taking into account individual differences.

Effect of nanocapsules containing docosahexaenoic acid in mice with chronic inflammation

BackgroundOmega 3 fatty acids, such as docosahexaenoic acid (DHA) have been widely consumed as supplements to control chronic inflammation. Nanocapsules containing DHA (MLNC-DHA-a1) were developed and showed excellent stability. Thus, our objective was to evaluate the effect of MLNC-DHA-a1 nanocapsules on biomarkers of chronic inflammation. MethodsCells viability was determined by flow cytometry. The uptake of MLNC-DHA-a1 nanocapsules by macrophages and their polarization were determined. In vivo, LDLr(-,-) mice were fed a Western diet to promote chronic inflammation and were treated with MLNC-DHA-a1 nanocapsules, intravenously injected via the caudal vein once a week for 8 weeks. ResultsMLNC-DHA-a1 nanocapsules decreased the concentration of TNFα (p = 0.02) in RAW 264.7 cells compared to the non-treated group (NT), with no changes in IL-10 (p = 0.29). The nanocapsules also exhibited an increase in the M2 (F4/80+ CD206) phenotype (p < 0.01) in BMDM cells. In vivo, no difference in body weight was observed among the groups, suggesting that the intervention was well tolerated. However, compared to the CONT group, MLNC-DHA-a1 nanocapsules led to an increase in IL-6 (90.45 ×13.31 pg/mL), IL-1β (2.76 ×1.34 pg/mL) and IL-10 (149.88 ×2.51 pg/mL) levels in plasma. ConclusionMLNC-DHA-a1 nanocapsules showed the potential to promote in vitro macrophage polarization and were well-tolerated in vivo. However, they also increased systemic pro-inflammatory cytokines. Therefore, considering that this immune response presents a limitation for clinical trials, further studies are needed to identify the specific compound in MLNC-DHA-a1 that triggered the immune response. Addressing this issue is essential, as MLNC-DHA-a1 tissue target nanocapsules could contribute to reducing chronic inflammation.

Pharmacokinetics, quorum-sensing signal molecules and tryptophan-related metabolomics of the novel anti-virulence drug Fluorothiazinon in a Pseudomonas aeruginosa-induced pneumonia murine model

Pseudomonas aeruginosa (PA) infection is commonly associated with hospital-acquired infections in patients with immune deficiency and/or severe lung diseases. Managing this bacterium is complex due to drug resistance and high adaptability. Fluorothiazinon (FT) is an anti-virulence drug developed to suppress the virulence of bacteria as opposed to bacterial death increasing host’s immune response to infection and improving treatment to inhibit drug resistant bacteria. We aimed to evaluate FT pharmacokinetics, quorum sensing signal molecules profiling and tryptophan-related metabolomics in blood, liver, kidneys, and lungs of mice. Study comprised three groups: a group infected with PA that was treated with 400 mg/kg FT (“infected treated group”); a non-infected group, but also treated with the same single drug dose (“non-infected treated group”); and an infected group that received a vehicle (“infected non-treated group”). PA-mediated infection blood pharmacokinetics profiling was indicative of increased drug concentrations as shown by increased Cmax and AUCs. Tissue distribution in liver, kidneys, and lungs, showed that liver presented the most consistently higher concentrations of FT in the infected versus non-infected mice. FT showed that HHQ levels were decreased at 1 h after dosing in lungs while PQS levels were lower across time in lungs of infected treated mice in comparison to infected non-treated mice. Metabolomics profiling performed in lungs and blood of infected treated versus infected non-treated mice revealed drug-associated metabolite alterations, especially in the kynurenic and indole pathways.

The Effect of Inhaled Ciclesonide Treatment on Systemic Markers of Immune Function in Horses

The use of dexamethasone to control equine asthma is a common and effective treatment. Although short-term systemic dexamethasone treatment has not been shown to induce systemic immunosuppression in the horse, the goal of this study was to determine whether inhaled ciclesonide, an FDA-approved drug for the treatment of equine asthma, exerts any systemic immunosuppressive effects when compared to dexamethasone-treated and untreated horses. Eighteen light, mixed breed horses, ranging in age from 3 to 8 years of age, were used for this study and randomly assigned to one of three treatment groups: (1) nontreated controls, (2) ciclesonide treatment, or (3) dexamethasone treatment. Blood was collected daily for steady-state messenger RNA (mRNA) analysis, as well as at Days 0, 5, 10, and 15 of treatment for in vitro stimulation with Concanavalin A (ConA). Messenger RNA relative quantities were determined using RT-qPCR for select genes. Two-way, repeated measures analysis of variance was used to analyze qPCR data and results considered significant at P < .05. There were significant decreases in the steady-state, whole-blood expression of granzyme B and interferon-γ due to dexamethasone treatment, when compared to the nontreated control group. Within ConA-stimulated samples, there remained a suppressive effect of dexamethasone treatment on granzyme B expression compared to nontreated control horses. Similar effects were not noted in the ciclesonide-treated horses. Significant effects of ciclesonide treatment on markers of immune function were not noted in this study, suggesting a low risk for immunosuppression with inhaled ciclesonide treatment.

MAIT cells confer resistance to Lenvatinib plus anti-PD1 antibodies in hepatocellular carcinoma through TNF-TNFRSF1B pathway

The combination of antiangiogenic agents and immune checkpoint inhibitors is more efficient than monotherapy in the management of hepatocellular carcinoma (HCC). Lenvatinib plus anti-PD1 antibodies have become the mainstay in HCC treatment. However, more than half the patients with HCC are non-responsive, and the mechanisms underlying drug resistance are unknown. To address this issue, we performed single-cell sequencing on samples from six HCC patients, aiming to explore cellular signals and molecular pathways related to the effect of lenvatinib plus anti-PD1 antibody treatment. GSVA analysis revealed that treatment with lenvatinib plus anti-PD1 antibody led to an increase in the TNF-NFKB pathway across all immune cell types, as compared to the non-treatment group. Mucosal-associated invariant T (MAIT) cells were found to secrete TNF, which activates TNFRSF1B on regulatory T cells, thereby promoting immunosuppression. Additionally, TNFSF9 was highly expressed in anticancer immune cells, including CD8+ effector T cells, MAIT, and γδ T cells in the treatment group. We also detected CD3+ macrophages in both HCC and pan-cancer tissues. Overall, our findings shed light on the potential mechanisms behind the effectiveness of lenvatinib plus anti-PD1 antibody treatment in HCC patients. By understanding these mechanisms better, we may be able to develop more effective treatment strategies for patients who do not respond to current therapies.

Proteomic profile of epidermal mucus from Labeo rohita reveals differentially abundant proteins after Aeromonas hydrophila infection

We report the proteomic profile of Epidermal Mucus (EM) from Labeo rohita and identified the differentially abundant proteins (DAPs) against Aeromonas hydrophila infection through label-free liquid chromatography-mass spectrometry (LC-MS/MS). Using discovery-based proteomics, a total of 2039 proteins were quantified in nontreated group and 1,328 proteins in the treated group, of which 114 were identified as DAPs in both the groups. Of the 114 DAPs, 68 proteins were upregulated and 46 proteins were downregulated in the treated group compared to nontreated group. Functional annotations of these DAPs shows their association with metabolism, cellular process, molecular process, cytoskeletal, stress, and particularly immune system. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Fisher's exact test between the two groups shows that most of the proteins were immune-related, which were significantly associated with the proteasome, phagosome, and Salmonella infection pathways. Overall, this study shows a basic and primary way for further functional research of the involvement of vitellogenin 2, alpha-2-macroglobulin-like protein, toll-like receptors (TLR-13), calpain, keratin-like proteins, and heat shock proteins against bacterial infection. Nonetheless, this first-ever comprehensive report of a proteomic sketch of EM from L. rohita after A. hydrophila infection provides systematic protein information to broadly understand the biological role of fish EM against bacterial infection.

Effectiveness of ivermectin and moxidectin against cyathostomins in four horse breeding farms in Mexico

This study aimed to evaluate the effectiveness of oral ivermectin and moxidectin against natural cyathostomin infection in four horse farms located in the central regions of Mexico. 445 horses of the Warmblood (145), Thoroughbreds (100), and Quarter Horses (200) breeds, aged between 6 months and 27 years, were used. Data on horses and parasite control methods were collected through interviews with farm owners and veterinarians. Using the McMaster technique, fecal samples were processed from all 445 horses, 180 of which were positive for cyathostomins. On each farm, a selection was made of 45 animals meeting the criteria of a Fecal Egg Count Reduction Test yielding results exceeding 150 eggs per gram of strongylid-type nematodes. Subsequently, three separate experimental groups were formed for each farm, each consisting of 15 horses The first group was treated with oral ivermectin 1.87 %; the second group with oral moxidectin 2 %; and the third was the non-treatment control group. Coprocultures were also performed to identify the presence of nematode species. The data obtained were analyzed with RESO.exe©️. Three of the four farms achieved a 100 % reduction in eggs per gram with both macrocyclic lactones. One farm achieved 93 % reduction with ivermectin and 87 % with moxidectin. This study demonstrates that macrocyclic lactones effectively reduce cyathostomins in three of the four farms studied. The results suggest potential cyathostomin resistance to macrocyclic lactones, particularly moxidectin, on one farm. Given these findings, sustainable parasite management is required on horse breeding farms in Mexico.

Potential role of the cell-penetrating peptide-conjugated soluble N-ethylmaleimide-sensitive factor attachment protein receptor motif of vesicle-associated membrane protein 2-patterned peptide in novel cosmeceutical skin product development.

This study aimed to investigate and verify the effect of cell-penetrating peptide (CPP)-conjugated soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) motif of vesicle-associated membrane protein 2 (VAMP2)-patterned peptide (INCI name: Acetyl sh-Oligopeptide-26 sh-Oligopeptide-27 SP, trade name: M.Biome-BT) on improving skin function in vitro. The cytotoxicity of CPP-conjugated SNARE motif of VAMP2-patterned peptide (CVP) was investigated using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay against B16-F10 cells and human dermal fibroblasts (HDFs) and a reconstructed skin irritation test. The anti-wrinkle activity of M.Biome-BT was determined by assessing the release of norepinephrine and dopamine in PC-12 cells via ELISA. The skin-whitening effects of CVP were assessed in B16-F10 cells by measuring the intra- and extracellular melanin contents and expression levels of melanin production-related genes, such as microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and TRP-2. CVP is not cytotoxic to B16-F10 cells and HDFs, and no skin irritation was observed. CVP treatment considerably diminished K+ -induced norepinephrine and dopamine secretion compared with the non-treated control group (62% and 40%, respectively). Additionally, the inhibition ability of CVP on norepinephrine and dopamine release was comparable to that of botulinum neurotoxin type A (BoNT/A). CVP also increased intracellular melanin content in a dose-dependent manner, whereas extracellular melanin content decreased (76%-85%). However, CVP treatment did not affect the mRNA expression of MITF, TYR, TRP-1, and TRP-2. These results suggest that CVP does not inhibit melanin production; however, it may induce a whitening effect by inhibiting melanin transport. Taken together, our findings indicate that CVP could be used as an active and safe cosmeceutical ingredient for antiaging applications.

Chitosan hydrogels with MK2 inhibitor peptide-loaded nanoparticles to treat atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that lacks ideal long-term treatment options due to a series of side effects, such as skin atrophy, related to the most common treatment prescribed to manage moderate-to-severe AD. In this study, a cell-penetrating MK2 inhibitor peptide YARA (YARAAARQARAKALNRQGLVAA) was loaded into hollow thermo-responsive pNIPAM nanoparticles (NP), which were further incorporated into chitosan hydrogels (H-NP-YARA) to promote local drug delivery, improve moisture and the anti-inflammatory activity. The NPs exhibited high loading efficiency (>50%) and the hydrogel remained porous following NP incorporation as observed by scanning electron microscopy (SEM). Both nanoparticles and hydrogels were able to improve the release of YARA and sustained release to up to 120 h. The hydrogels and NPs delivered 2 and 4-fold more YARA into viable skin layers of porcine skin in vitro at 12 h post-application than the non-encapsulated compound in intact and impaired barrier conditions. Furthermore, the YARA-loaded NPs (NP-YARA) and H-NP-YARA treatment decreased the levels of inflammatory cytokines up to 20 time-fold compared with the non-treated group of human keratinocytes under inflammatory conditions. Consistent with the results in cell culture, the loading of YARA in NP reduced the levels of IL-1β, IL-6, and TNF-α up to 3.3 times in an ex vivo skin culture model after induction of inflammation. A further decrease of up to 17 times-fold was observed with H-NP-YARA treatment compared to the drug in solution. Our data collectively suggest that chitosan hydrogel containing YARA-loaded nanoparticles is a promising new formulation for the topical treatment of AD.

Association between Patient Experience Scores and Low Utilization of Hepatocellular Carcinoma Treatment in the United States: A Surveillance, Epidemiology, and End Results–Consumer Assessment of Healthcare Providers and Systems Analysis (SEER-CAHPS)

PurposeTo study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States. Materials and MethodsUsing Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002–2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items. ResultsAmong 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment. ConclusionsHCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD.

How correlations between treatment access and surveillance inclusion impact neglected tropical disease monitoring and evaluation-A simulated study.

Neglected tropical diseases (NTDs) largely impact marginalised communities living in tropical and subtropical regions. Mass drug administration is the leading intervention method for five NTDs; however, it is known that there is lack of access to treatment for some populations and demographic groups. It is also likely that those individuals without access to treatment are excluded from surveillance. It is important to consider the impacts of this on the overall success, and monitoring and evaluation (M&E) of intervention programmes. We use a detailed individual-based model of the infection dynamics of lymphatic filariasis to investigate the impact of excluded, untreated, and therefore unobserved groups on the true versus observed infection dynamics and subsequent intervention success. We simulate surveillance in four groups-the whole population eligible to receive treatment, the whole eligible population with access to treatment, the TAS focus of six- and seven-year-olds, and finally in >20-year-olds. We show that the surveillance group under observation has a significant impact on perceived dynamics. Exclusion to treatment and surveillance negatively impacts the probability of reaching public health goals, though in populations that do reach these goals there are no signals to indicate excluded groups. Increasingly restricted surveillance groups over-estimate the efficacy of MDA. The presence of non-treated groups cannot be inferred when surveillance is only occurring in the group receiving treatment.

Is administration of anti-MRSA drugs recommended for patients with pneumonia when MRSA is isolated from respiratory specimens? A systematic review and meta-analysis

It is unclear whether anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs should be uniformly administered to patients with pneumonia when MRSA is isolated from respiratory specimens. A systematic review was conducted to evaluate the efficacy of the uniform administration of anti-MRSA drugs. Two researchers independently searched the literature as of December 2022, extracted relevant papers, and performed a meta-analysis. The outcomes were mortality and adverse events. No applicable randomized controlled trials were found during the study period, but four observational studies were extracted. The relative risk of mortality in the anti-MRSA group was 1.67 [95% confidence interval 0.65–4.30], which did not differ significantly from the non-administered group. Further investigation into the background of patients demonstrated that anti-MRSA drugs were administered to groups in which only MRSA was cultured. However, the pneumonia severity index did not differ from that in the non-treated group. No studies of adverse events were found. Our review did not find a beneficial contribution to mortality from uniform anti-MRSA medication to patients with pneumonia when MRSA was isolated from respiratory specimens. Factors determining risk-based individualized treatment should be validated as the future question.

Platelet-rich plasma as an ideal biomaterial for improving pregnancy of infertility mice

Uterine implantation failure can be caused by uterine pathologies, including endometrial thinning or adhesions. This investigation aims to evaluate the effect of platelet-rich plasma (PRP) on endometrial regeneration. In this study, a double-dose non-activated PRP therapy was administered by repeatedly infusing a similar volume of non-activated PRP 24 h after the first dose in the in vitro damaged endometrial tissue models and in vivo injured uterine models. Histology, implantation, and pregnancy assessments of endometrial structure and function were performed. We discovered that in the in vitro models, the treated endometrial tissues appeared to have endometrial epithelium, uterine glands, pinopodes, and embryos that were able to implant on the endometrium. The rate of implanted embryos in the treated models was 18.89% ± 0.02 higher than those in the non-treated group with no embryo implantation (P-value <0.05). Animal models also showed similar results. The uterine structure was restored, the number of glands (143.3 ± 9.815) and the thickness (rate of endometrial area (EA)/total horn area (THA) was 0.4013 ± 0.0344) were increased in the treated models (P-value <0.05). The number of pregnancies (implantation sites) in the treated mouse models was 10.33 ± 1.53. In conclusion, double-dose non-activated PRP could effectively promote endometrial regeneration.

The combined effects of probiotic CLOSTAT® and Aviboost® supplement on growth performance, intestinal morphology, and immune response of broiler chickens

The present study assessed the effects of dietary supplementation of probiotic CLOSTAT®, alone or in combination with Aviboost® supplement, on growth performance, intestinal histomorphology, and immune response in broiler chickens. A total of 600 one-day-old broiler chicks were divided into three groups: G1 (non-treated negative control group), G2 (probiotic CLOSTAT®- and Aviboost®-treated group), and G3 (probiotic CLOSTAT®- treated group). Feed intake and mean body weight were measured weekly for all groups. Sera were collected for cytokine analysis, and duodenal samples were also collected for histomorphological examination. The results revealed that the mean body weight gain was significantly increased to 2.25 and 2.2 kg/bird in G2 and G3, respectively, compared to 1.95 kg/bird in G1. Similarly, the feed conversion ratio (FCR) was improved to 1.56 and 1.59 in G2 and G3, respectively, compared to 1.8 in G1. Serum interferon-γ (IFN-γ) and interleukin (IL)-6 protein concentrations were significantly increased in G2 and G3 compared to G1. Furthermore, the absorptive cells of the villi revealed structural changes, including hyperplasia and increased goblet cell population and microvilli height, in G2 and G3 compared to G1. The lamina propria of duodenal villi in G2 and G3 showed increased cellularity at 22 days of age. In conclusion, the individual supplementation of CLOSTAT® and Aviboost® led to enhanced performance, intestinal morphology, and immune response. While their simultaneous supplementation slightly improved the body weight gain and FCR but did not exhibit synergistic or additive effects on intestinal morphology and systemic immune response.

Longitudinal follow-up of bladder function in children who participated in the Swedish Reflux Trial

Several publications have reported the coexistence of vesicoureteral reflux (VUR) and bladder dysfunction in children. Whether this dysfunction remains in the longer term is not yet known. This study revisited children who participated in the Swedish Reflux Trial (SRT) with the primary aim of evaluating whether bladder and bowel dysfunction (BBD) in these patients persisted until adolescence. The secondary aim was to evaluate two BBD subgroups, and relations to recurrent urinary tract infections (UTI). Of the 161 eligible children at SRT study-end, 73 children participated. Their bladder function was evaluated longitudinally using a validated BBD questionnaire with symptom score (cut-off ≥7) and uroflowmetry, at five (T2) and ten years (T3) after study-end. T1 was the SRT study-end. Besides BBD, the sub-diagnoses overactive bladder (OAB) and dysfunctional voiding symptoms (DVS) were calculated from symptom scores. BBD was diagnosed in 37% of children at mean age 3.7 years, which decreased with age to 23% of adolescents (mean age 15.7). DVS and OAB subgroups were equally common at T1, but only DVS was identified at the last follow-up (T3) (p=0.0008). Recurrent UTIs were seen in 17% at T3 and were more common in patients with BBD (p=0.038). The gender distribution of BBD also changed, from being equally common at the end of the SRT to affecting mainly adolescent girls at the last follow-up (p=0.022). Information was available regarding VUR status after repeat VCUGs during follow-up in 22 patients, 12 of them after endoscopic treatment. An improvement in VUR grade was found in the 22, but during follow-up numbers with BBD or UTI did not differ between treated and non-treated groups. The prevalence of BBD decreased from 37% at 3-4 years of age to 23% in adolescence, when it was almost exclusively seen in girls. BBD and the subgroup DVS were associated with UTI. Even if epidemiological studies have established a predisposition to bladder symptoms and UTI in girls, little is known about bladder function in adolescents with a history of VUR during the first years of life. One limitation of the study was the number of patients participating. Also, the number of patients with kidney damage was more common in the cohort. In this longitudinal follow-up of BBD in children with VUR, the number of children with BBD decreased with age. In adolescence, both BBD and recurrent UTIs mainly affected girls.

Frequency-coded patterns of sympathetic vasomotor activity are differentially evoked by the paraventricular nucleus of the hypothalamus in the Goldblatt hypertension model.

The paraventricular nucleus of the hypothalamus (PVN) contains premotor neurons involved in the control of sympathetic vasomotor activity. It is known that the stimulation of specific areas of the PVN can lead to distinct response patterns at different target territories. The underlying mechanisms, however, are still unclear. Recent evidence from sympathetic nerve recording suggests that relevant information is coded in the power distribution of the signal along the frequency range. In the present study, we addressed the hypothesis that the PVN is capable of organizing specific spectral patterns of sympathetic vasomotor activation to distinct territories in both normal and hypertensive animals. To test it, we investigated the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), before and after disinhibition of the PVN by bicuculline microinjection. Subjects were control and Goldblatt rats, a sympathetic overactivity-characterized model of neurogenic hypertension (2K1C). Additionally, considering the importance of angiotensin II type 1 receptors (AT1) in the sympathetic responses triggered by bicuculline in the PVN, we also investigated the impact of angiotensin AT1 receptors blockade in the spectral features of the rSNA and sSNA activity. The results revealed that each nerve activity (renal and splanchnic) presents its own electrophysiological pattern of frequency-coded rhythm in each group (control, 2K1C, and 2K1C treated with AT1 antagonist losartan) in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the losartan 2K1C treated group showed no decrease in the hypertensive response triggered by bicuculline when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups (control and 2K1C), suggesting that the blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic responses nor the electrophysiological patterns in Goldblatt rats, but act on their spectral frequency distribution. The results suggest that the differential responses evoked by the PVN were preferentially coded in frequency, but not in the global power of the vasomotor sympathetic responses, indicating that the PVN is able to independently control the frequency and the power of sympathetic discharges to different territories.

Medicaid Expansion Is Associated With Increases in Medicaid-Funded Total Joint Arthroplasty

BackgroundExisting literature presents competing views concerning the impact of Medicaid expansion on total joint arthroplasty (TJA) utilizations. While some reports demonstrate that expansion does not increase Medicaid acceptance by surgeons, others show increases in Medicaid-funded TJA via limited analyses. We conducted a nationwide, multi-insurance, econometric study to determine if Medicaid-funded and all-funding-source total hip arthroplasty (THA) or total knee arthroplasty (TKA) utilizations increased following expansion. MethodsThis study examined 999,015 THA and 2,099,975 TKA from 2010 to 2017 using a commercially available national payer database. Difference-in-differences analyses, econometric regression methods used to assess the impact of policy change, were used to examine the impact of Medicaid expansion on TJA utilizations, and event analyses were used to confirm the parallel trends assumption, which helps to ensure that the estimated effect is not a result of existing differences in trends between treatment and nontreatment groups. ResultsEvent analyses confirmed parallel trends in the pre-expansion period. Difference-in-differences analyses found a persistent increase in Medicaid-funded THA (40.4%, P = .001, confidence interval [CI]: 12.7, 62.1%), but not THA from all funding sources (4.6%, P = .128, CI: −1.3, 10.8%). Medicaid-funded TKA (35.8%, P < .001, CI: 17.4, 68.0%) increased, but not TKA from all funding sources (3.4%, P = .321, CI: −3.1, 10.1%). ConclusionWhile the number of Medicaid-funded TJAs increased, expansion had no significant effect when examining all funding sources. This suggests that Medicaid expansion primarily affected source of TJA funding, not overall volume. Further research is needed to examine state-specific predictors of response to Medicaid expansion.

Cerebrolysin recovers diaphragmatic function and reduces injury-associated astrogliosis following a cervical spinal cord hemi-section injury in rats

BackgroundSpinal cord injury (SCI) is widely considered the most disastrous medical condition. With no available treatment to date, SCI continues to cause disabilities to the patients and affect their own and their caregivers' quality of life. Cerebrolysin (CBL) is a neuropeptide preparation derived from purified brain proteins with suggested neuroprotective and neurotrophic properties. CBL showed earlier the ability to target multiple pathways that helped in the improvement of the recovery following different groups of neurological diseases and injuries, including ischemic stroke, traumatic brain injuries, and even neurodegenerative diseases. In the current study, the neuroprotective effect of CBL following a SCI is called into question using a rat model of spinal cord cervical hemi-section validated earlier by our lab and others. Using 32 rats divided into four groups randomly, CBL treatment was implemented for either 7 or 21 days duration, following the cervical spinal cord hemi-section.ResultsFollowing the CBL treatment, rats with cervical cord hemi-section showed functional improvement of diaphragmatic muscle as recorded by electromyography (EMG). In addition, the histopathological assessment of the spinal cord showed improved neuronal viability and reduced astrogliosis at the site of the injury compared to the non-treated group. 21-day treatment showed significant improvement when compared to the shorter 7-day regimen.ConclusionOur data suggest that CBL is capable of protecting and regenerating anterior horn motor neurons with functional recovery of diaphragmatic muscle functions in rats, suggesting the potential use of CBL for future regenerative and neuroprotective therapy following SCI.

Machine learning-based radiotherapy time prediction and treatment scheduling management.

The utility efficiency of medical devices is important, especially for countries such as China, which have a large population and shortage of medical care resources. Radiotherapy devices are among the most valuable and specialized equipment categories and carry enormous treatment loads. In this study, a novel method is proposed to improve the efficiency of a radiotherapy device (linac). Although scheduling management with accurate prediction of the entire treatment time included in each appointment, arrange a reasonable time duration for appointments and save time between patient shifts effectively. Tasks belonging to the treatment and non-treatment groups can be assigned more flexibly based on the availability of time. Data from 1665 patients, including patient positioning time (PT) and treatment time (TT), were collected in collaboration with the Radiotherapy Center of the Department of Oncology at the Second Affiliated Hospital of Kunming Medical University from November 2020 to August 2021. The features related to PT and TT were extracted and used to train the machine learning-based model to predict PT and TT in independent patients. The prediction results were subsequently applied to a minute-based scheduling tool. Artificial intelligence is a promising approach to solve abstract problems with a specialized knowledge background. The results of this study show encouraging prediction outcomes in relation to effective scheduling management and could improve the efficiency of the linac. This successful trial broadens the meaning of medical data and potential future research directions in radiotherapy.

Heterogeneous treatment effects of adjuvant therapy for patients with cervical cancer in the intermediate-risk group.

The efficacy of adjuvant therapy for patients with cervical cancer with intermediate risk (CC-IR) remains controversial. We examined the impact of adjuvant therapy on survival outcomes in patients with CC-IR and evaluated the heterogeneous treatment effects (HTEs) of adjuvant therapies based on clinicopathologic characteristics. We retrospectively analyzed a previous Japanese nationwide cohort of 6192 patients with stage IB-IIB cervical cancer who underwent radical hysterectomy. We created two pairs of propensity score-matched treatment/control groups to investigate the treatment effects of adjuvant therapies: (1) adjuvant therapy versus non-adjuvant therapy; (2) chemotherapy versus radiotherapy conditional on adjuvant therapy. Multivariate analyses with treatment interactions were performed to evaluate the HTEs. Among the 1613 patients with CC-IR, 619 and 994 were in the non-treatment and treatment groups, respectively. Survival outcomes did not differ between the two groups: 3-year progression-free survival (PFS) rates were 88.1% and 90.3% in the non-treatment and treatment groups, respectively (p = 0.199). Of the patients in the treatment group, 654 and 340 received radiotherapy and chemotherapy, respectively. Patients who received chemotherapy had better PFS than those who received radiotherapy (3-year PFS, 90.9% vs. 82.9%, p = 0.010). Tumor size was a significant factor that affected the treatment effects of chemotherapy; patients with large tumors gained better therapeutic effects from chemotherapy than those with small tumors. Adjuvant therapy is optional for some patients with CC-IR; however, chemotherapy can be recommended as adjuvant therapy, particularly for patients with large tumors.