Observation Time Points Research Articles

Thyroglobulin levels in COVID-19-positive patients: Correlations with thyroid function tests, inflammatory markers, and glucocorticoid use.

COVID-19 often results in generalized inflammation and affects various organs and systems. Endocrine research focused on the possible sequelae of COVID-19, with special interest given to the thyroid gland. Clinical problems such as thyroid function in non-thyroidal illness (NTI), autoimmune thyroiditis, and COVID-19-related subacute thyroiditis (SAT) quickly gained wide coverage. Thyrotoxicosis of various origins leads to the release of peripheral thyroid hormones and thyroglobulin (TG), the main glycoprotein contained within the thyroid follicular lumen. In our study, we evaluated TG levels in COVID-19-positive patients and investigated the possible relationships between TG, thyroid function tests (TFTs), and inflammatory markers. Our approach included separate subanalyses of patients who received and those who did not receive glucocorticoids (GCs). In the entire population studied, the concentration of TG tended to decrease with time (p<0.001; p1,2 = 0.025, p1,3 = 0.001, p2,3 = 0.003), and this pattern was especially clear among patients treated with GCs (p<0.001; p1,2=<0.001; p1,3=<0.001; p 2,3=<0.001). The concentration of TG differed significantly between patients treated and those not treated with GC at the second and third time points of observation (p=0.033 and p=0.001, consecutively). TG concentration did not differ between the patients with normal and abnormal TFTs. The correlations between TG, TFTs, and inflammatory markers were very limited. 19 patients had elevated TG levels, but a TFT pattern suggestive of thyrotoxicosis was not common in this group. There were no statistically significant differences between patients who met and those who did not meet the predefined combined primary endpoint.

Commentary: Consensual ophthalmotonic reaction.

Intraocular pressure (IOP) change in the untreated fellow eye accompanied by a corresponding IOP reduction in the operated eye has been identified as the “consensual ophthalmotonic reaction” (COR), and the terminology was coined by Weekers in 1924.[1] This response was initially observed after contusion, ocular compression, tonography, and cauterization of the sclera.[2] In 1927, Wilmer published the first report on COR after a fistulating surgery in experimental animals.[3] After that, multiple studies have reported the possibility of IOP variation in the fellow eye following unilateral glaucoma surgery, including not only trabeculectomy, but glaucoma drainage device implantations, filtering canaloplasty, and microshunt implantations as well.[4] However, whether there is an IOP increase, decrease, or no change in the fellow eye after glaucoma surgery is still controversial. These contrasting results could be due to differences in the type of glaucoma, preoperative IOP, surgical technique, antimetabolite dosage and duration, time point of observation, and outflow facility of the untreated fellow eye. The postulated mechanisms behind COR include neuronal, hormonal, and cytokine regulation of aqueous flow dynamics.[5] Nevertheless, the exact mechanism is yet to be elucidated. A decrease in IOP in the fellow eye could be associated with improved patient compliance to the antiglaucoma therapy or the effect of systemic absorption of the medications. Also, it could result from a “regression to the mean” effect, as trabeculectomy is often planned when the IOP is high on the variation curve.[6] Regarding COR with topical medications, Newman et al.[7] observed that the IOP reduction in contralateral eyes was found to be associated with timolol only and not prostaglandins or carbonic anhydrase inhibitors. A similar decrease in IOP in the fellow eye has also been reported after laser trabeculoplasty, which might be due to the effects of the systemic release of humoral agents, such as matrix metalloproteinase, and improved medication compliance.[8] An increase in the fellow eye IOP following glaucoma surgery has been observed in the present study. We have also observed an IOP rise in a significant number of patients in the unoperated eye in the early postoperative period after unilateral trabeculectomy, though we do not have published data. Different theories have been postulated that may explain this finding. Weekers[1] explained the possible existence of COR in which activation of the nervous system increased the fellow eye aqueous production. Diestelhorst and Krieglstein[5] also postulated that unilateral filtration surgery triggers a central nervous system-mediated reflective increase in aqueous flow in the unoperated fellow eye to maintain physiological stability. In an animal experiment, a supraoptic controlling pathway has been suggested to lead to an IOP rise in response to water drinking after unilateral optic nerve sections.[9] A few studies described that underperfusion of the trabecular meshwork by aqueous humor in the operated eye and increased extracellular trabecular meshwork material deposition induces a reflex mechanism mediated by specialized cells in the scleral spur that can lead to decreased outflow in the fellow eye.[10] Another hypothesis was an increase in the prostaglandin level in response to the inflammation in the operated eye.[11] Other possible explanations include a postoperative presumed steroid response or withdrawal of antiglaucoma medications.[12] No studies have attributed the increase in IOP in the fellow eye to one factor. In the literature, post-surgical COR is found to occur at an earlier time frame than post-laser COR, which might suggest the role of mechanical triggers rather than chemical triggers in post-surgical COR. The predominance of one mechanism occurring due to a particular intervention may guide the IOP varia tion in the contralateral eye. Further prospective studies and a much more detailed macroscopic overview are needed to delineate the underlying mechanisms and the exact biological role of post-surgical COR. The take-home message is that the fellow eye needs to be carefully monitored after unilateral glaucoma surgery. The fellow eye may be the only eye with vision or the better eye of the two. Also, fellow eyes may be already glaucomatous, that failure to monitor and recognize IOP rise may delay appropriate management leading to glaucoma progression. It is recommended to inform the patient about the possibility of IOP variation in the other eye after glaucoma surgery and the need for multiple visits, especially in the early postoperative period. Another relevant message is that the fellow eyes should not be preferably used as a control in studies assessing the IOP outcomes of a particular treatment or intervention.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Novel Animal Model of Limbal Stem Cell Deficiency Induced by Forcing Eye-Open at Birth.

The aim of this study was to develop a rat model of limbal stem cell deficiency (LSCD) by forcing eye-open at birth (FEOB). A total of 200 Sprague-Dawley neonatal rats were randomly divided into the control group and the experimental group, which received eyelid open surgery on postnatal day 1 (P1). Observation time points were defined as P1, P5, P10, P15, and P30. Slit-lamp microscope and corneal confocal microscope were used to observe the clinical features of the model. The eyeballs were collected for hematoxylin and eosin staining and periodic acid-Schiff staining. Proliferating cell nuclear antigen, CD68/polymorphonuclear leukocytes, and cytokeratin 10/12/13 immunostaining were performed, while the ultrastructure of the cornea was observed by scanning electron microscopy. Real-time polymerase chain reactions (PCRs), western blot, and immunohistochemical staining of activin A receptor-like kinase-1/5 were used to analyze the possible pathogenesis. FEOB could successfully induce the typical manifestations of LSCD, including corneal neovascularization, severe inflammation, and corneal opacity. In the FEOB group, goblet cells could be detected in the corneal epithelium by periodic acid-Schiff staining. The expression of cytokeratins was also different between the 2 groups. Furthermore, proliferating cell nuclear antigen immunohistochemical staining revealed the weak proliferation and differentiation ability of limbal epithelial stem cells in the FEOB group. Real-time PCRs, western blot, and immunohistochemical staining of activin A receptor-like kinase-1/activin A receptor-like kinase-5 in the FEOB group showed different expression patterns than those of the control group. FEOB in rats induces ocular surface changes resembling LSCD in humans, representing a novel model of LSCD.

Generation of monoclonal antibodies against PBP2a to improve diagnosis and potential treatment of MRSA infections

Background: MRSA is a type of MDR bacterium. All around the world, it leads to significant nosocomial and community-acquired diseases. The discovery of fresh ideas is very important because there are so few effective treatments for MRSA infections. PBP2a is a great candidate for the development of MRSA-specific Mabs. Aim: The purpose of this study was to create murine Mabs against PBP2a in order to enhance MRSA laboratory detection and possibly treatment. Methods: Anti-PBP2a MAb was tested for biodistribution, therapeutic, and preventative effects in comparison to vancomycin. After receiving anti-PBP2a MAb therapy, biodistribution was assessed between 12 and 96 hours later. Results: During the observation timepoints, the majority of the generated MAb stayed in the serum and just a tiny fraction was found in the kidneys, lungs, and spleen. A prophylactic experiment in mice given the lethal dosage 50 (LD50) found that treated animals with anti-PBP2a MAb had a greater survival rate than the control group. In a therapeutic experiment, one dosage of anti-PBP2a MAb reduced bacterial load in the kidneys similarly to the group treated with five doses of vancomycin, and a combination therapy with anti-PBP2a MAb and vancomycin was more effective than either drug used alone. Conclusion: The findings of this study suggested that an anti-PBP2a MAb may be extremely useful in the creation of innovative diagnostic tools and promising treatments for preventative and therapeutic measures against MRSA infections.

Evaluation of perfusion index as an objective indicator of successful interscalene block

Background: Interscalene nerve blocks are commonly performed for surgeries of the upper limb. Assessment methods for evaluation of blocks are conventional and subjective. Aims and Objectives: The aim of the study was to evaluate perfusion index (PI) as an objective indicator for assessing successful ultrasound guided interscalene block. Materials and Methods: This prospective, observational study included adult patients undergoing upper limb surgery (humerus and shoulder) under USG guided interscalene nerve block. PI was recorded at baseline (before LA administration), at every 2 min till 10 min, and then every 5 min till 30 min after the block in both the arms. The PI values were compared between the blocked and unblocked arms at all observed time points. PI ratio was calculated as the ratio between PI at 15 min after block and the baseline PI. Results: The PI increased significantly in the blocked limb after local anesthetic injection and there was a statistically significant difference in PI values between the blocked and unblocked arms at all-time points. Both PI and PI ratio at 15 min after injection showed a sensitivity and specificity of 100% for block success at cutoff values of 3.2 and 2.04, respectively. Conclusion: PI maybe used as an objective indicator of successful interscalene nerve block. PI &gt;3.2 and PI ratio &gt;2.04 at 15 min are accurate predictors for block success.

Efficacy and Safety of 4.7 mg Deslorelin Acetate Implants as a Neutering Option in Male Cats: A Large-Scale Multicentre Randomised Controlled Study.

This multicenter-controlled, double-masked randomized European study was conduc-ted to confirm both the efficacy and safety of a deslorelin implant in controlling fertility and sexual behavior in a large population of tom cats over a 12-month period. Among the 225 screened individuals, a total of 205 privately owned indoor intact male cats, aged 3 months of age or older, were randomly allocated to a deslorelin implant (n = 154) or to a negative control group (n = 51). After the screening visit performed between day (D)-14 and D-7, six additional visits were sche-duled on D0, D45, D93, D186, D279 and D372. Effects on testosterone, sexual behaviors, penile spines, testicular volume and intact male cat urine odor were assessed at every visit under masked conditions as regards to the treatment group. In addition, phone calls from the investigators to the owners were scheduled on D7 and then on a monthly basis whenever no visit was scheduled. Success was defined as an individual serum testosterone concentration below or equal to 0.10 ng/mL and was 77.9% at D45, 83.1% at D93, 84.4% at D186 and D279, and 61.7% at D372 in the deslorelin group, and 3.9% at D45, 5.9% at D93, 3.9% at D186, 7.8% at D279 and 3.9% at D372 in the negative control group. Testing for superiority was made stepwise from D45 to D372 upwards; the difference in success rates was significant from D45 to D372 (p < 0.001 for each time point). The mean testosterone concentration dropped from baseline in the deslorelin group, remaining below the set threshold of 0.1 ng/mL until D372. From D7 onwards, the mean sum score for sexual behaviors (including vocalization, urine marking, aggression and intact male cat urine odor) was significantly lower at each observation time point in the deslorelin group compared to the control group, where no decrease in scores was observed. The mean percent change to baseline of the testicular volume and the percentage of cats with a decreased visibility and adult appearance of penile spines were significantly lower in the deslorelin group as soon as D45. No relevant safety concerns were reported during the course of the study. The deslorelin implant Suprelorin® 4.7 mg (Virbac, Carros, France) is a safe and effective neutering option, inducing infertility over a 12-month period when administered to intact male cats aged between 3 months of age and 11 years of age. The implants also successfully reduced sexual behaviors (i.e., vocalization, urine marking, aggression), intact male cat urine odor, testicular volume and penile spine score for 1 year (372 ± 5 days).

In vitro evaluation of Aloe saponaria as a potential feed additive to modulate ruminal fermentation and microbial diversity

ABSTRACT Saponin possessed antiprotozoal activity; therefore, it is generally used to mitigate enteric methane (CH4) emission in ruminant nutrition. The objective of this study was to evaluate the effects of Aloe saponaria (AS) supplementation on rumen fermentation, CH4, and microbial diversity in an in vitro experiment over 48 h incubation. Five treatments were used: (1) no additives (CON), 1% and 2% dosage of heat-dried AS (HAS), and freeze-dried AS (FAS), and the experiments were performed three times. After the incubation, volatile fatty acids (VFAs), CH4 proportion in total gas, and microbial diversity were evaluated. Gas production was assessed at 3, 6, 9, 12, 24, 36, and 48 h incubation. FAS addition significantly increased gas production compared to CON except for 6 and 48 h, whereas HAS addition did not significantly affect the gas production at all observed time points. AS addition significantly increased total VFA and the absolute abundances of fungi and Ruminococcus albus regardless of drying method. There was no significant change in the CH4 proportion at 48 h, although the reduction in ciliate protozoa was detected in FAS-treated groups. In conclusion, FAS may be an effective feed additive to improve ruminal fermentation via enhancing feed utilization by rumen microbes.

The Impact of Robotic Fractionated Radiotherapy for Benign Tumors of Parasellar Region on the Eye Structure and Function.

To evaluate the radiation effect of fractionated robotic radiotherapy of benign tumors located in the parasellar region on the anterior and posterior segments of the eye. A prospective observational study based on the expanded ophthalmological examination. The pre-treatment baseline was used as a control for the post-radiotherapy follow-up examinations. The study group consists of 34 patients (68 eyes) irradiated using the CyberKnife system. There were ten patients with cavernous sinus meningioma, nine with pituitary adenoma, five with meningioma of the anterior and middle cranial fossa, five with meningioma in the region close to optic chiasm, three with craniopharyngioma, and two with meningioma of the orbit. All patients were treated using three fractions of 600-800 cGy. We assessed the impact of radiation on the eye based on changes in anatomical and functional features. The condition of the eye surface, central corneal thickness (CCT), endothelial cell density (ECD), lens densitometry, central macular thickness (CMT), and retinal nerve fiber layer (RNFL) were the anatomical features assessed. The functional tests were best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) and visual-evoked potentials (VEP). An ophthalmologic examination was performed before and 6, 12, 18, and 24 months after radiotherapy. We did not observe any significant changes in BCVA, IOP, CCT, CMT, VF, and VEP, nor in the slit-lamp examination during the two-years observation. We found a significant decrease in ECD at all follow-up measurements. The drop in ECD exceeded approximated age-related physiological loss. The reduction in ECD was not large enough to disrupt corneal function and thus affect vision. We also observed a statistically significant reduction of RNFL in all observation time points. However, there was no correlation between the dose delivered to the optic pathway and the decrease in RNFL thickness. The thinning of the RNFL was not significant enough to impair visual function. Fractionated robotic radiotherapy of the tumors located close to the optical pathway is safe and does not impair patient's vision. Minor changes found in optic nerve anatomy (RNFL thinning) might be related to radiation effect or tumor compression. The causal relation between low doses of radiation delivered to the cornea and the observed significant but slight decrease in ECD is uncertain. The observed changes did not cause visual disturbances perceivable by the patients.

TED-Trazodone Efficacy in Depression: A Naturalistic Study on the Efficacy of Trazodone in an Extended-Release Formulation Compared to SSRIs in Patients with a Depressive Episode-Preliminary Report.

These are the preliminary results of a 12-week non-randomized, open-label, non-inferiority study comparing the effectiveness of trazodone in an extended-release formulation (XR) versus SSRIs in the treatment of major depressive disorder (MDD). Participants (n = 76) were recruited, and 42 were assigned to the trazodone XR group and 34 to the SSRIs group. The choice of drug was based on clinical presentation and relied upon the attending physician. Assessments were made at five observation time points, at the following weeks: 0, and after 2, 4, 8, and 12 weeks. The evaluations included: symptoms of depression (MADRS, QIDS-clinician, and self-rated versions-primary study endpoints), anhedonia (SHAPS), anxiety (HAM-A), insomnia (AIS), psychosocial functioning (SDS), and therapeutic efficacy (CGI). At baseline, the trazodone group had significantly more severe depressive, anxiety, and insomnia symptoms and worse psychosocial functioning compared to the SSRIs group. After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of insomnia and depression. There were no differences between the groups in the frequencies of therapeutic response and remission, which indicated the non-inferiority of the trazodone XR treatment. In conclusion, our results showed that in a "real world" setting, trazodone XR is effective in the treatment of patients with MDD.

Valuing equity-linked death benefits with a threshold expense structure under a regime-switching Lévy model

&lt;p style='text-indent:20px;'&gt;In this paper, we investigate the valuation problem of equity-linked death benefits with a threshold expense structure. Specifically, a regime-switching Lévy process is used to describe the underlying asset price process, which is monitored periodically. The fees are assumed to be continuously deducted at some constant rate from the policyholder's account between the current and next monitoring times, if the account value is smaller than a pre-specified level at the current observation time point. Under the modified threshold expense structure, some explicit valuation expressions for life-contingent call options are derived by the Fourier cosine series expansion method. Numerical results demonstrate the accuracy and efficiency of our method.&lt;/p&gt;

Comparative evaluation of postoperative pain after single-visit endodontic treatment using protaper gold and hyflex electrical discharge machining rotary file system

Background: Endodontics has a widened range due to its increase in success rate and increase in lifespan of individuals. As of today, extracting the tooth has become a rare situation, and endodontic intrusion has become a custom. Although after having detailed knowledge about the internal anatomy of tooth, it is a must to know about the upcoming evolution of instruments as well as materials and complete knowledge regarding techniques of treatment modalities. Postoperative pain could leave a significant control on the quality of life, which will begin after completion of endodontic treatment having a range of 3%–58% cases. Materials and Methods: Twenty-six patients with irreversible pulpitis were selected for single-visit endodontics. The teeth were blindly assigned to two groups based on the instrumentation systems used: Group A (Protaper Gold) and Group B (Electrical Discharge Machining [EDM] Hyflex). Participants were asked to note the incidence of preand postoperative pain on the Visual Analog Scale at different time intervals. Results: The greatest mean pain in both Group A and B was found to be maximum in the first 24 h, with a significant reduction in pain at the subsequent observation time points of 48 h, 72 h, and 7 days. The least painful group was Group A, followed by Group B. Conclusion: In single-visit endodontics, both Protaper Gold and EDM Hyflex both may prove to be a better system, but according to statistics Protaper gold being slightly superior as it produces minimal postoperative pain, thus improving the overall acceptance of endodontic treatment.

Study on the efficacy and safety of foldable capsular vitreous body in the severe retinal detachment eyes

BackgroundThis study was to evaluate the efficacy and safety of the implantation of foldable capsular vitreous body (FCVB) in severe retinal detachment eyes.MethodsA retrospective study in retinal detachment eyes was performed at Shandong Provincial Hospital Affiliated to Shandong First Medical University. A standard three-port pars plana vitrectomy was performed, and the FCVB was triple folded and implanted into the vitreous cavity. The silicone oil (SO) was then injected into the capsule of the FCVB to support the retina and eye. During the follow-up period, The treated eyes were examined by ophthalmoscopy, fundus photography, and tonometry. B-scan ultrasonography, optical coherence tomography (OCT), and computed tomography (CT), were also performed.ResultsFrom May 2020 to November 2021, 31 cases with severe retinal detachment were enrolled in the study. The postoperative follow-up time gradient ranged from 1 to 72 weeks, At various observation time points during the 72 weeks after surgery, The postoperative IOP was maintained at around 10 mmhg at various time points, with a slight decrease compared to the preoperative IOP (14.2 ± 4.6 mmHg n = 18), and was statistically significant. 9 of 31 patients had clear refractive media, both fundus and OCT showed retinal reattachment, OCT showed the 200 μm thick FCVB capsule support retina. The remaining 22 patients with unclear refractive media, B-scan showed arcuate hyperechoes in front of the retina. There was also no significant difference in visual acuity compared to preoperative. The FCVB was well positioned in the vitreous cavity, and no serious complications such as endophthalmitis, glaucoma, silicone oil emulsification, product exposure, or sympathetic uveitis were found.ConclusionsFCVB has retinal support with certain ability to maintain IOP and eye morphology and avoid eye removal in patients with severe retinal detachment during the 72-week observation period.

Chloroquine treatment influences immunologicalmemory through the PD-1/PD-L1 pathway during the initiation of Plasmodium chabaudi infection.

Growing evidence describes the host immune response mechanism involved in malaria. Despite the spread of drug resistance, chloroquine (CQ) remains the main antimalarial drug in most countries in Latin America and Asia. Studies have indicated an immunomodulatory activity of CQ, however, the potential implications for CQ on immunological memory recognizing the malaria parasite are still being elucidated. Our study suggests that CQ treatment significantly delayed the initiation of parasitemia during infection of mice with the rodent malaria parasite, Plasmodium chabaudi (P.c.). Additionally, there was a decrease in T follicular helper cells (Tfh), CD4+ effector memory T cells, memory B cells (MBC), IgG2a memoryB cells, along with IgG2a plasma cells; while antibody production was not affected atthe observation time points. After PD-1 blockade and CQ treatment, no reductions in the numbers of CD4+ effector memory T cells, MBC, and IgG2a memoryB cells were observed compared with the P.c. group. Therefore, CQ might regulate immunological memory via the PD-1/PD-L1 signaling pathway. Compared with antibody secretion, the inhibition of CQ on immune memory cells was a more sensitive indicator.

Was size of healthcare institution a factor affecting changes in healthcare utilisation during the COVID-19 pandemic in Korea? A retrospective study design analysing national healthcare big data

ObjectivesMany small-sized healthcare institutions play a critical role in communities by preventing infectious diseases. This study examines how they have been impacted by the global COVID-19 pandemic compared with large...

Bayesian Analysis of First-Order Markov Models for Autocorrelated Binary Responses.

In many clinical trials, patient outcomes are often binary-valued which are measured asynchronously over time across various dose levels. To account for autocorrelation among such longitudinally observed outcomes, a first-order Markov model for binary data is developed. Moreover, to account for the asynchronously observed time points, nonhomogeneous models for the transition probabilities are proposed. The transition probabilities are modeled using B-spline basis functions after suitable transformations. Additionally, if the underlying dose-response curve is assumed to be non-decreasing, our model allows for the estimation of any underlying non-decreasing curve based on suitably constructed prior distributions. We also extended our model to the mixed effect model to incorporate individual-specific random effects. Numerical comparisons with traditional models are provided based on simulated data sets, and also practical applications are illustrated using real data sets.

Revascularization character of autologous fascia lata graft following shoulder superior capsule reconstruction by enhanced magnetic resonance imaging

BackgroundFascia lata has been used for arthroscopic superior capsule reconstruction (ASCR) and verified to achieve a good clinical outcome. However, it is still not known about revascularization character of the fascia lata after ASCR. This study was performed to evaluate the revascularization of autologous fascia lata grafts after ASCR by enhanced magnetic resonance imaging (MRI).MethodsA prospective study of 19 patients with irreparable rotator cuff tears underwent ASCR with autologous fascia lata grafts from September 2019 to April 2021. Radiography examinations and clinical evaluations were performed preoperatively and postoperatively at 6 weeks and 3, 6, and 12 months. The signal-to-noise quotient (SNQ) value and enhancement index (EI) of autologous fascia lata grafts in the great tubercle insertion (GTI), midpoint of the graft (MG), and glenoid insertion (GI) were compared for radiography examination. Clinical evaluation included the American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) shoulder score, and Visual Analog Scale (VAS) score.ResultsThe SNQ values in T1WI enhancement at GI and GTI were significantly higher than those at the plain MRI scan at all postoperative observation timepoints; however, the SNQ values in T1WI enhancement at MG did not show a significant difference until 3 months postoperation. EI values at GTI and GI were significantly higher than those at MG at 6 weeks and 3 months postoperation, while there was no significant difference in the EI value between GTI and GI. At 6 months postoperation, the EI value at GI was significantly higher than those at MG. At 12 months postoperation, the EI value at GI was significantly higher than those at MG and GTI; however, there was no significant difference between GTI and MG. The EI values at GTI and MG peaked at 3 months and 6 months postoperation, respectively, and then plateaued at 12 months postoperation. However, there was no significant difference in the EI value among the different postoperative timepoints at GI. The EI value did not correlate with the VAS and ASES, UCLA scores at any time point or any postoperative observation location.ConclusionRevascularization of the fascia lata was dependent on the location of the fascia lata and plateaus at 12 months postoperation. The EI value did not correlate with the VAS and ASES, UCLA scores during12 months postoperation.

Danlu tongdu tablets: Preclinical safety evaluation and mechanism of hepatotoxicity.

Danlu tongdu tablets (DLTD) is a listed Chinese patent medicine collected in the Pharmacopoeia of the People's Republic of China (version 2020). This prescription has been applied in clinics in China for lumbar spinal stenosis and lumbosacral disc herniations. The wide application of Danlu tongdu in therapy has raised some clinical adverse reactions, such as significant elevation of alanine transaminase (ALT) and aspartate transaminase (AST) in individual patients after use. The present study aimed to investigate the safety of Danlu tongdu and analyze its adverse effects on the liver. The maximum feasible dose (MFD) was used to carry out the acute toxicity tests. Mortality, adverse effects, body weight and food consumption were recorded for up to 14days post treatment. In the 6-month chronic toxicity test, sprague-dawley rats were randomly divided into four groups according body weight, the experimental groups were administrated to rats at the concentrations of 1.67, 3.34 and 6.67g/kg/day, whereas the control group was received the ultrapure water (vehicle) only, 10ml/kg, once a day. The animal's body weight, food consumption was monitored weekly. In addition, their hematological and biochemical parameters, body and organ weights and histopathology, were all measured at specific observation time points. Additionally, we further explored the adverse effects mechanism of Danlu tongdu on the liver through transcriptome analysis. No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 1.67g/kg and 3.34g/kg, respectively. We found that mild hypertrophy and hyperplasia of hepatic interlobular bile ducts were detected in some rats with doses of 6.67g/kg after repeated oral administration of Danlu tongdu for 13 and 26weeks, but the above changes in liver were reversible. The results of transcriptome sequencing showed that Danlu tongdu had a significant effect on cytochrome P450 enzymes in rat liver, especially cytochrome P450 1 (CYP1) subtype. Therefore, the toxic target organ of Danlu tongdu is the liver and the mechanism of mild liver injury is closely related to the up-regulation of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression.

Usefulness of the Kinect-V2 System for Determining the Global Gait Index to Assess Functional Recovery after Total Knee Arthroplasty.

The Korean Knee Society (KKS) score is used for functional evaluation during follow-up after total knee arthroplasty (TKA), but it is time-consuming to measure and is limited by its subjective nature. We investigated whether the global gait asymmetry index (GGA) that can be obtained using the Kinect-V2 system could overcome the KKS limitations. Forty-three patients who underwent TKA from January 2019 to December 2019 were included. Postoperatively, regular follow-up was performed at 2, 4, 6, 8, and 12 weeks, and at 4, 6, and 12months. At each follow-up visit, the KKS was measured, and the walking path was followed with six Kinect-V2 systems. After allowing the participants to walk naturally, the range of motion of each joint of the lower extremity and GGA were obtained. Changes in the KKS and GGA scores and measurement times were investigated until the final follow-up. A statistical model was made to predict the KKS from the GGA score using data at all observed time points, and analysis of variance (ANOVA) with Turkey's post-hoc tests and Pearson correlation tests were used for evaluation. Both the KKS and GGA scores improved significantly from 4 weeks postoperatively until the final follow-up. The measurement time was significantly shorter for the GGA (9.3 ± 1.4min) than for the KKS (32.4 ± 9.2min; P < 0.001) score. The predicted and actual KKS values clustered close to a straight line on the scatter plot, but the prediction was less accurate in the initial stage (2 weeks post-surgery) than at later time points. The mean absolute error (MAE) and root mean square of the error (RMSE) were considered to be poorly predicted in the initial stage (8 weeks post-surgery) compared to the later time-points (MAE ≥ 5 and RMSE ≥ 6 for 8 weeks post-surgery). In the early phase after knee joint surgery (up to 12 weeks post-surgery), the GGA index does not predict the KKS well. However, after this time point, the GGA index can be simply measured in the outpatient department and may be able to replace the KKS. Thus, evaluation of the GGA index using the Kinect-V2 may be a useful method to evaluate functional recovery in the outpatient clinic after knee joint surgery.

Intervention of the Mahuang Lianqiao Chixiaodou decoction on immune imbalance in atopic dermatitis-like model mice

To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis (AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction (MLCD) on skin damage and inflammation factors in an AD-like mouse model. Ninety-six male BALB/c mice were divided into normal, model, positive control (mometasone furoate), and traditional Chinese medicine treatment (MLCD) groups by a random number table. 2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group. The treatment or intervention was administered for seven consecutive days on days 4, 18, 32, and 39. The mRNA relative expressions of interleukin-4 (IL-4), IL-10, interferon-γ (IFN-γ), thymic stromal lymphopoietin (TSLP), and the TSLP receptor (TSLPR) were measured using quantitative real-time polymerase chain reaction, and the serum immunoglobulin E, IL-4, IL-10, and IFN-γ levels were detected using enzyme-linked immunosorbent assay. Compared with the normal group, the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11, 25, and 39. Compared with the model group, the epidermal thickness of the positive control group was significantly alleviated on day 39 ( P < .001), and that of the MLCD group was significantly improved on days 25 and 39 ( P < .001). Compared with the four observation time points, MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions. On day 39, compared with the model group, MLCD downregulated the skin mRNA relative expressions of IL-4 ( P = .009), TSLP ( P = .030), and TSLPR ( P < .001), and reduced the mouse serum levels of IL-4 ( P = .003). For other serum indicators, no significant difference was observed between the model and MLCD groups. MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.