Post-treatment Group Research Articles

A Comparative Analytical and Invivo Evaluation of Musta (Cyperus Rotundus Linn.) and Shatavari (Asparagus Racemosus Wild.) for Anti Atherosclerotic Activity

Obesity and hyperlipidemia are predisposing factors for major number of cardiovascular diseases, especially Atherosclerosis which has become the major cause for death. Sthoulya is a Medo pradoshaja vikara. Hyperlipidemia and Atherosclerosis can be correlated to Rasa pradoshaja vikara and Dhamani Prathichaya respectively. The treatment advocated for all the three conditions is Kaphahara and Medohara. Out of the big list of Kaphamedohara dravyas, Musta and Shatavari are two Dravyas with dissimilar Rasapanchakas that needs to be evaluated for the specific activity and indication. Analytical studies of the drugs were carried out as per the standard protocol. Invivo evaluation of Churna, Aqueous and Methanolic extracts of both the drugs in High fat diet induced Atherosclerosis were carried out on New Zealand White rabbits in both preventive and curative aspects. Though both the drugs were effective, Shatavari showed significant result in reducing Blood glucose, Total Cholesterol, Triglycerides, LDL and VLDL in comparison with Musta. Churna and Aqueous extract of Shatavari were effective than methanolic extract. Musta was found better in reducing the body weight in post treatment group than Shatavari. Churna and Methanolic extract of Musta were effective than aqueous extract in the reduction of body weight, Total cholesterol, Triglycerides, LDL and VLDL. Except body weight in pretreatment, the drugs were effective in both preventive and curative aspects. Musta is drug of choice in obesity associated with hyperlipidemia where as Shatavari would be effective in hyperlipidemia associated with Rasa kshaya lakshanas. Both Musta and Shatavari have potential Antiatherosclerotic activity.

Evaluation of a single dose of intra-testicular insulin treatment in heat-stressed mice model.

Insulin plays important role in testicular functions such as germ cell proliferation and steroidogenesis, despite its conventional role as a hypoglycaemic agent. It is also well known that testicular activity is severely get affected by heat stress and heat stress induces testicular pathogenesis. The effect of insulin on heat-induced testicular impairment has not been investigated. Thus, it is hypothesized that insulin might modulate testicular activity in a heat-stressed model. Experimental mice were separated into 4 groups; the first group was the normal control (CN), and the second group was subjected to heat stress (HS) by submerging the lower body part in a thermostatically controlled water bath maintained at 43°C for 15 min. The third and fourth groups were treated with a single dose of intra-testicular insulin (0.6IU/mice) before and after heat stress. Animal tissue samples were collected after 14 days of heat treatment. Insulin treatment did not improve the sperm parameters; however, both insulin pre and post-treatment improved the markers of spermatogenesis such as Johnsen score, germinal epithelium height and the number of stages VII/VIII. The histoarchitecture of testis also showed amelioration from heat-induced pathogenesis in the insulin-treated groups. Insulin treatment has also increased the proliferation of germ cells (increased PCNA and GCN), survival (Bcl2), and decreased apoptosis (active caspase-3). Furthermore, insulin treatment decreased MDA levels, without pronounced effects on the activities of antioxidant enzymes. Heat stress also decreased the circulating testosterone and oestrogen levels, and insulin treatment significantly increased oestrogen levels only. Although testosterone showed an increasing trend, it was insignificant. The expression of aromatase, AR, ER-α, and ER-β was down regulated by heat-stress and insulin treatment up regulated these markers. In conclusion, our results showed the amelioration of heat-induced testicular impairment by pre and post-intra-testicular insulin treatments. Insulin-associated improvements in the pre-and post-treatment groups suggested a preventive mechanism of insulin against heat stress in the testis.

The effect of discharge planning on the stability of blood sugar levels in type 2 diabetes mellitus patients

Introduction: Diabetes mellitus (DM) is a serious threat to human health in the 21st century, Indonesia as a developing country has a high number of sufferers. This study aims to analyze the effect of discharge planning on the stability of blood sugar levels in type 2 patients. Methods: The design of this study was a Quasi-Experimental Pre and Post-test with a Control Group. The population in this study were all patients with type 2 DM, a large sample of 54 respondents, taken by purposive sampling technique. The instruments used are a glucometer, questionnaire, and discharge planning form. Data analysis used Wilcoxon statistical test for pre-treatment and control groups and the Mann-Whitney test for post-treatment and post-control. Results: The results of the Wilcoxon statistical test pre-post-treatment obtained = 0.000 and pre-post-control obtained = 0.093. The results of post-treatment and control group obtained = 0.009 and value = 0.05. It means that there is an effect of discharge planning on the stability of blood sugar levels in type 2 DM patients at A. Yani Islamic Hospital, Surabaya. Conclusion: The conclusion of this study is discharge planning can affect the stability of blood sugar levels in patients with diabetes mellitus type 2.

Acceptance-enhanced behavior therapy for trichotillomania in adults: A randomized clinical trial

Given the limited treatment options for trichotillomania (TTM), or Hair Pulling Disorder, this large randomized clinical trial evaluated the efficacy of acceptance-enhanced behavior therapy for TTM (AEBT-TTM) in reducing TTM severity relative to psychoeducation and supportive therapy (PST). Eighty-five adults (78 women) with TTM received 10 sessions (over 12 weeks) of either AEBT-TTM or PST. Independent evaluators masked to treatment assignment assessed participants at baseline (week 0), midpoint (week 6), and endpoint (week 12). Consistent with a priori hypotheses, 64% of the adults treated with AEBT-TTM were classified as clinical responders at post-treatment relative to 38% treated with PST. Clinical responders were identified by a score of 1 or 2 on the Clinical Global Impressions-Improvement (CGI-I) scale. Relative to the PST group, the AEBT-TTM group demonstrated significantly greater pre-to post-treatment reductions on the self-report Massachusetts General Hospital-Hairpulling Scale (MGH-HS) and the evaluator-rated National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS). There were no significant post-treatment group differences on the Clinical Global Impressions-Severity (CGI-S) scale, or rate of TTM diagnoses. Results suggest AEBT-TTM provides greater treatment benefit than PST. Future research should continue to investigate AEBT-TTM along with mediators and moderators of its efficacy.

Characteristics of salivary microbiota in children with obstructive sleep apnea: A prospective study with polysomnography.

ObjectivesThe present study aimed to investigate the characteristics of salivary microbiota of children with obstructive sleep apnea (OSA) and to assess longitudinal alterations in salivary microbiota before and after adenotonsillectomy.MethodsA set of cross-sectional samples consisted of 36 OSA children (17 boys and 19 girls, 7.47 ± 2.24 years old) and 22 controls (9 boys and 13 girls, 7.55 ± 2.48 years old) were included in the study, among which eight OSA children (five boys and three girls, 8.8 ± 2.0 years old) who underwent treatment of adenotonsillectomy were followed up after 1 year. Saliva samples were collected, and microbial profiles were analyzed by bioinformatics analysis based on 16S rRNA sequencing.ResultsIn cross-sectional samples, the OSA group had higher α-diversity as estimated by Chao1, Shannon, Simpson, Pielou_e, and observed species as compared with the control group (p < 0.05). β-Diversity based on the Bray–Curtis dissimilarities (p = 0.004) and Jaccard distances (p = 0.001) revealed a significant separation between the OSA group and control group. Nested cross-validated random forest classifier identified the 10 most important genera (Lactobacillus, Escherichia, Bifidobacterium, Capnocytophaga, Bacteroidetes_[G-7], Parvimonas, Bacteroides, Klebsiella, Lautropia, and Prevotella) that could differentiate OSA children from controls with an area under the curve (AUC) of 0.94. Linear discriminant analysis effect size (LEfSe) analysis revealed a significantly higher abundance of genera such as Prevotella (p = 0.027), Actinomyces (p = 0.015), Bifidobacterium (p < 0.001), Escherichia (p < 0.001), and Lactobacillus (p < 0.001) in the OSA group, among which Prevotella was further corroborated in longitudinal samples. Prevotella sp_HMT_396 was found to be significantly enriched in the OSA group (p = 0.02) with significantly higher levels as OSA severity increased (p = 0.014), and it had a lower abundance in the post-treatment group (p = 0.003) with a decline in each OSA child 1 year after adenotonsillectomy.ConclusionsA significantly higher microbial diversity and a significant difference in microbial composition and abundance were identified in salivary microbiota of OSA children compared with controls. Meanwhile, some characteristic genera (Prevotella, Actinomyces, Lactobacillus, Escherichia, and Bifidobacterium) were found in OSA children, among which the relationship between Prevotella spp. and OSA is worth further studies.

A comprehensive analysis of miRNA/isomiRs profile of hydrosalpinx patients with interventional ultrasound sclerotherapy.

Hydrosalpinx is a chronic inflammatory condition with high recurrence rate, and it is reported among female population having fallopian tubal factor infertility. Previously, we have reported that interventional ultrasound sclerotherapy improves endometrial receptivity and pregnancy rate with negligible adverse effects in patients suffering from hydrosalpinx. During present investigation, we have used next generation sequencing (NGS) to characterize the isomiR profiles from the endometrium of patients suffering from hydrosalpinx before and after interventional ultrasound sclerotherapy. Our results indicated that miRNA arm shift and switch remained unaffected when compared in patients before and after interventional ultrasound sclerotherapy. We observed that isomiRs with trimming at 3’ and isomiRs with canonical sequences were lower in post-treatment than in pre-treatment group. Gene ontology (GO) annotation and KEGG pathway analysis revealed that the expression of mature mir-30 was significantly lower in the pre-treatment as compared to post treatment group while the expression of mir-30 isomiR was 4.26-fold higher in pre-treatment when compared with the post-treatment group. These different expression patterns of mir-30 mature miRNA and mir-30 isomiRs in two groups are affecting the physiological function of the endometrium. Our results suggested that differential isomiR distribution in hydrosalpinx patients before and after treatment plays an important role in hydrosalpinx incidence and can help in designing novel strategy for the treatment of hydrosalpinx in female population.

Branched-Chain Amino Acids Are Neuroprotective Against Traumatic Brain Injury and Enhance Rate of Recovery: Prophylactic Role for Contact Sports and Emergent Use

Branched-chain amino acids (BCAAs) are known to be neurorestorative after traumatic brain injury (TBI). Despite clinically significant improvements in severe TBI patients given BCAAs after TBI, the approach is largely an unrecognized option. Further, TBI continues to be the most common cause of morbidity and mortality in adolescents and adults. To date, no study has evaluated whether BCAAs can be preventive or neuroprotective if taken before a TBI. We hypothesized that if BCAAs were elevated in the circulation before TBI, the brain would readily access the BCAAs and the severity of injury would be reduced. Before TBI induction with a standard weight-drop method, 50 adult mice were randomized into groups that were shams, untreated, and pre-treated, post-treated, or pre- + post-treated with BCAAs. Pre-treated mice received BCAAs through supplemented water and were dosed by oral gavage 45 min before TBI induction. All mice underwent beam walking to assess motor recovery, and the Morris water maze assessed cognitive function post-injury. On post-injury day 14, brains were harvested to assess levels of astrocytes and microglia with glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) immunohistochemistry, respectively. Pre-treated and pre- +post-treated mice exhibited significantly better motor recovery and cognitive function than the other groups. The pre- + post-treated group had the best overall memory performance, whereas the pre-treated and post-treated groups only had limited improvements in memory compared to untreated animals. Pre- + post-treated brains had levels of GFAP that were similar to the sham group, whereas the pre-only and post-only groups showed increases. Although trends existed, no meaningful changes in IBA-1 were detected. This is the first study, animal or human, to demonstrate that BCAA are neuroprotective and substantiates their neurorestorative benefits after TBI, most likely through the important roles of BCAAs to glutamate homeostasis.

Comparing the Effect of Stretching and Muscle Energy Technique in the Management of Lower Cross Syndrome

Aim: To compare the effects of stretching exercises &amp; muscle energy techniques in the management of lower cross syndrome. Methods: In this parallel, randomized controlled trail fifty-eight patients were randomly assigned into two intervention groups. Group A received stretching technique and Group B received muscle energy technique, three sessions per week for total duration of four weeks. Results: Normality test applied and P values were noted by applying Shapiro-Wilk test both groups. Baseline measures for both groups showed no significant difference as the P value &gt; 0.05. The paired t-test within the group of Stretching and Muscle Energy Technique showed significant difference in pre and post Numeric Pain Rating Scale (NPRS), pre and post Oswestry Disability Index (ODI) and pre and post muscle length via inclinometer and goniometer. Independent t-test for post treatment groups between stretching group and muscle energy technique group was not significant i.e. P&gt; 0.05. Conclusion: The study concluded that statistically there is no significant difference in variables of both groups i.e. Numeric Pain Rating Scale (NPRS), Oswestry Disability Index (ODI), bilateral muscle length of iliopsoas, hamstrings and rectus femoris as well as of erector spinae. However, mean values of above mentioned parameters show a little more improvement in Muscle Energy Technique group. Keywords: Stretching, Muscle Energy Technique, Lower Cross Syndrome, Muscle imbalance.

Detection of distant metastases and distant second primary cancers in head and neck squamous cell carcinoma: comparison of [18F]FDG PET/MRI and [18F]FDG PET/CT

PurposeThis prospective study aimed to compare the diagnostic performance of [18]FDG PET/MRI and PET/CT for the detection of distant metastases and distant second primary cancers in patients with head and neck squamous cell carcinoma (HNSCC).MethodsA total of 103 [18F]FDG PET/MRI examinations immediately followed by PET/CT were obtained in 82 consecutive patients for staging of primary HNSCC (n = 38), suspected loco-regional recurrence/follow-up (n = 41) or unknown primary HNSCC (n = 3). Histology and follow-up > 2 years formed the standard of reference. Blinded readers evaluated the anonymized PET/MRI and PET/CT examinations separately using a 5-point Likert score. Statistical analysis included: receiver operating characteristic (ROC) analysis, jackknife alternative free-response ROC (JAFROC) and region-of-interest (ROI)-based ROC to account for data clustering and sensitivity/specificity/accuracy comparisons for a score ≥ 3.ResultsDistant metastases and distant second primary cancers were present in 23/103 (22%) examinations in 16/82 (19.5%) patients, and they were more common in the post-treatment group (11/41, 27%) than in the primary HNSCC group (3/38, 8%), p = 0.039. The area under the curve (AUC) per patient/examination/lesion was 0.947 [0.927–1]/0.965 [0.917–1]/0.957 [0.928–0.987] for PET/MRI and 0.975 [0.950–1]/0.968 [0.920–1]/0.944 [0.910–0.979] for PET/CT, respectively (p > 0.05). The diagnostic performance of PET/MRI and PET/CT was similar according to JAFROC (p = 0.919) and ROI-based ROC analysis (p = 0.574). Sensitivity/specificity/accuracy for PET/MRI and PET/CT for a score ≥ 3 was 94%/88%/89% and 94%/91%/91% per patient, 96%/90%/91% and 96%/93%/93% per examination and 95%/85%/90% and 90%/86%/88% per lesion, respectively, p > 0.05.ConclusionsIn HNSCC patients, PET/MRI and PET/CT had a high and similar diagnostic performance for detecting distant metastases and distant second primary cancers.

Effect of Combined Intraosseous and Intraarticular Infiltrations of Autologous Platelet-Rich Plasma on Subchondral Bone Marrow Mesenchymal Stromal Cells from Patients with Hip Osteoarthritis.

Osteoarthritis (OA) is a debilitating condition that significantly impacts its patients and is closely associated with advancing age and senescence. Treatment with autologous platelet rich plasma (PRP) is a novel approach that is increasingly being researched for its effects. Subchondral bone mesenchymal stromal cells (MSCs) are key progenitors that form bone and cartilage lineages that are affected in OA. This study investigated the changes in subchondral bone MSCs before and after combined intraosseous (IO) and intraarticular (IA) PRP infiltration. Patient bone marrow aspirates were collected from 12 patients (four male, eight female) aged 40–86 years old (median 59.5). MSCs were expanded in standard media containing human serum to passage 1 and analysed for their colony-forming potential, senescence status, and gene expression. Hip dysfunction and Osteoarthritis Outcome Score (HOOS) at baseline and 6 months post second infiltration were used to assess the clinical outcomes; seven patients were considered responders and five non-responders. The number of colony-forming MSCs did not increase in the post treatment group, however, they demonstrated significantly higher colony areas (14.5% higher compared to Pre) indicative of enhanced proliferative capacity, especially in older donors (28.2% higher). Senescence assays also suggest that older patients and responders had a higher resistance to senescent cell accumulation. Responder and non-responder MSCs tended to differ in the expression of genes associated with bone formation and cartilage turnover including osteoblast markers, matrix metalloproteinases, and their inhibitors. Taken together, our data show that in hip OA patients, combined IO and IA PRP infiltrations enhanced subchondral MSC proliferative and stress-resistance capacities, particularly in older patients. Future investigation of the potential anti-ageing effect of PRP infiltrations and the use of next-generation sequencing would contribute towards better understanding of the molecular mechanisms associated with OA in MSCs.

Royal jelly reduce DNA damage induced by alkylating agent in mice

Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct comet assays at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.

Comparison Of the Effectiveness of Maitland Manipulation of Thoracic Spine Versus Grade I And II Maitland Mobilization of Cervical Spine on Pain Intensity and Functional Status in Patients of Cervical Radiculopathy

Cervical radiculopathy (CR) is a most reported pathological problem mainly due to herniated disc material causing nerve compression or the formation of osteophytes. This impingement specifically causes cervical pain radiating to arm, numbness, and sensory deficit. It also affects the motor function of the neck and upper extremities. Objectives: To evaluate the comparative effectiveness of Maitland manipulation of thoracic spine versus grade I and II Maitland mobilization of cervical spine on Pain, intensity, and functional status in patients of cervical radiculopathy. Methods: Total 32 patients suffering from cervical radiculopathy were randomly assigned to receive Maitland manipulation on thoracic spine along with Conventional Physiotherapy (intermittent cervical traction, strengthening exercises) in Group A(n=16) and Maitland mobilization on cervical spines along with Conventional Physiotherapy in Group B (n=16). Total treatment sessions given to each group was 9 (3 sessions per week). To measure outcome numeric pain rating scale (NPRS) and neck disability index (NDI) questionnaire was used. Data collection was done at the beginning and post-treatment. Results: The study revealed that the mean age of patients was 47.59 with a range minimum of 27 years to a maximum of 59 years. Comparison of post-treatment of both groups showed mean NPRS score in group A (Maitland thoracic spine manipulation) was 4.56± 1.031 and group B (Maitland cervical spine mobilization) was 6.12± 0.50, while post-treatment NDI score group A was 22.44± 10.09 and group B was 36.88± 8.437 with p=0.000 that was p&lt;0.05. Conclusion: The study concluded that both Maitland thoracic spine manipulation and Maitland cervical spine mobilization techniques have similar effects in reducing cervical radiculopathy and increasing active range of motion. However, Maitland thoracic spine manipulation showed better results in neck pain reduction and improved functional status on the comparison.

Ganoderma lucidum mitigates gamma radiation-induced oxidative stress in Swiss albino mice

ObjectiveRadiotherapy is well established in cancer therapeutics. Though radiation targets tumor cells, they damage normal tissues by bystander effect. The present study aimed to evaluate the radioprotective efficacy of Ganoderma lucidum (GL) mycelium powder on gamma radiated swiss albino mice. Materials and methodQualitative phytochemical tests and in-vitro antioxidant activity of GL were carried out using standard protocols. Institutional animal ethical committee clearance was obtained. The pre and post-treated mice were irradiated using Gamma chamber 2000 (CARRT), Mangalore University. Biochemical estimations (TAC, SOD, NO, GPx, MDA, reduced glutathione), hematological markers (RBC, WBC, Hb, Platelet), lipid profile, inflammatory markers (Il-2, TNF-alpha, IF-gamma) and genotoxic markers (micronucleus and comet assay) were performed using standard protocols and commercially available kits. ConclusionThe pre and post-treatment groups showed statistically significant differences (p < 0.05) compared to radiation control in hematological parameters, lipid profile, micronucleus, and comet formation. In pre-treatment and post-treatment groups, Ganoderma lucidium mycelium extracts mitigated radiation-induced hematological, oxidative stress, hyperlipidemia, and genotoxic changes.

Molecular mechanism study of Astragalus adsurgens Pall synergistically induced by plasma and plasma-activated water

The mutagenic effects of discharge plasma and plasma+PAW (plasma and its activated water combined) on Astragalus adsurgens Pall seeds were explored. Needle array-plate dielectric-barrier discharge plasma was used to treat A. adsurgens Pall seeds and PAW was prepared at the same time. The deionized water and the obtained PAW were used to cultivate plasma-treated seeds in groups and the survival rate of each group was counted. Results showed that the survival rate of the treated seeds of A. adsurgens Pall when cultured with deionized water was not significantly different from that of the control check (CK). The culture with PAW had an obvious lethal effect and each group reached the half-lethal dose. Reactive oxygen species (ROS) and RNA-Seq analysis of seedlings in the 3 h treatment group showed that the content of ROS in the 3 d post-treatment group was significantly higher than that of the CK. Because expression of the gene with the function of scavenging superoxide free radicals was upregulated, the ROS content of seedlings on the sixth day was significantly lower than that on the third day. Plasma and plasma+PAW treatments changed a large number of gene expressions; particularly, the plasma+PAW group caused plant-growth genes to be significantly upregulated. After treatment, the seedlings of A. adsurgens Pall may grow faster and have higher nutritional value. This research is of great significance to the wider application of isoelectronic bodies and their activated water physicochemical mutagens in biological effects and breeding research.

Reliability of dynamic susceptibility contrast perfusion metrics in pre- and post-treatment glioma

BackgroundIn neuro-oncology, dynamic susceptibility contrast magnetic resonance (DSC-MR) perfusion imaging emerged as a tool to aid in the diagnostic work-up and to surveil effectiveness of treatment. However, it is believed that a significant variability exists with regard to the measured in DSC-MR perfusion parameters. The aim of this study was to assess the observer variability in measured DSC-MR perfusion parameters in patients before and after treatment. In addition, we investigated whether region-of-interest (ROI) shape impacted the observer variability.Materials and methodsTwenty non-treated patients and a matched group of twenty patients post-treatment (neurosurgical resection and post-chemoradiotherapy) were included. Six ROIs were independently placed by three readers: circular ROIs and polygonal ROIs covering 1) the tumor hotspot; 2) the peritumoral region (T2/FLAIR-hyperintense region) and 3) the whole tumor region. A two-way random Intra-class coefficient (ICC) model was used to assess variability in measured DSC-MRI perfusion parameters. The perfusion metrics as assessed by the circular and the polygonal ROI were compared by use of the dependent T-test.ResultsIn the non-treated group, circular ROIs showed good–excellent overlap (ICC-values ranging from 0.741–0.963) with the exception of those representing the tumor hotspot. Polygonal ROIs showed lower ICC-values, ranging from 0.113 till 0.856. ROI-placement in the posttreatment group showed to be highly variable with a significant deterioration of ICC-values. Furthermore, perfusion metric assessment in similar tumor regions was not impacted by ROI shape.DiscussionThis study shows that posttreatment quantitative interpretation of DSC-MR perfusion imaging is highly variable and should be carried out with precaution. Pretreatment assessment of DSC-MR images, however, could be carried out be a single reader in order to provide valid data for further analyses.

A comprehensive analysis of Glasgow Prognostic Score (GPS)/the modified Glasgow Prognostic Score (mGPS) on immune checkpoint inhibitor efficacy among patients with advanced cancer.

The association between Glasgow Prognostic Score (GPS) and the modified Glasgow Prognostic Score (mGPS) and clinical outcomes in patients receiving immune checkpoint inhibitors (ICIs) remains controversial. Thus, this meta-analysis aimed to examine the prognostic performance of GPS and mGPS in patients treated with ICIs. Eligible studies were retrieved from searches of EMBASE, PubMed, Web of Science, and Cochrane Library until July 2021. The hazard ratio (HR) and 95% confidence intervals (CIs) were pooled by using fixed-effect or random-effects model to evaluate the influence of GPS/mGPS on overall survival (OS) and progression-free survival (PFS). A total of 1164 patients were included. Overall, mGPS score of 2 and 1 were related to inferior OS (p < 0.001) and PFS (p < 0.001). Subgroup analyses showed no significant association between mGPS score of 1 and OS in patients with non-small cell lung cancer (NSCLC), while this score was significantly associated with poor PFS in patients with NSCLC and head and neck squamous cell carcinoma. Higher GPS (score of 1 or 2) were associated with poor clinical outcomes (OS: p < 0.001; PFS: p=0.036). Subgroup analysis showed high GPS levels were linked to worse OS in patients with NSCLC and gastric cancer, but not for PFS in these patients. Regarding test time point, GPS was related to worse OS and PFS in pre-treatment GPS group, but not in post-treatment GPS group. GPS and mGPS showed great potential to predict survival in patients treated with ICIs. Large and perspective trial are warranted to further validate these findings.

Plasma renin, aldosterone, and urinary prostaglandin E2 levels in children with hypocalcemia due to vitamin D deficiency rickets

We investigated the effect of hypocalcemia on plasma renin, aldosterone, and urine PGE2 levels in children with vitamin D deficiency rickets (VDDR). In the study group, 25 patients with VDDR-induced hypocalcemia were treated with a single dose of 150,000–300,000 IU cholecalciferol and 50 mg/kg/day elemental Ca for 10 days. On any day between 21th and 30th days after the treatment, the patients’ clinical, biochemical and radiologic findings were re-evaluated. The healthy children with the same sex and similar age as the study group comprised the control group. Plasma sodium (Na), potassium (K), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), 25- hydroxy vitamin D (25OHD), renin, aldosterone; and urinary Ca, creatinine (Cr) and prostaglandin E2 (PGE2) levels were measured in both the study (pre-treatment and post-treatment) and the control group. Plasma Ca, P, 25OHD and renin levels and urinary PGE2/Cr ratio in the post-treatment group were significantly higher than those in the pre-treatment group while K, ALP, and PTH concentrations were significantly lower. Plasma ALP and PTH levels in pre-treatment group were significantly higher than in the control group while Ca, P, 25OHD, aldosterone and renin concentrations and urinary PGE2/Cr ratio were significantly lower. Post-treatment plasma Ca level was significantly decreased in normal limits compared to the control group while other biochemical parameters were not different from the control group. Plasma Ca concentration was positively correlated with renin level and urinary PGE2/Cr ratio. The findings suggest that hypocalcemia may inhibit the production of renin, aldosterone and PGE2 and a blunt aldosterone secretion may develop even after recovery from hypocalcemia.

Long-term follow-up results of the effects of chronotherapy and conventional chemotherapy combined with intensity modulated radiotherapy on dendritic cells and lymphocyte subsets in nasopharyngeal carcinoma.

e18066 Background: In this study, we compared the effects of chronotherapy with conventional chemotherapy plus intensity modulated radiotherapy (IMRT)on dendritic cells and lymphocyte subsets in locoregionally advanced NPC. Methods: Analysis of 136 patients with treatment locoregionally advanced nasopharyngeal carcinoma enrolled, 68 patients were randomly assigned to the chronotherapy group and 68 patients to the conventional chemotherapy group, and all patients received 2-3 cycles of TPF induction chemotherapy plus 2-3 cycles of cisplatin concurrent chemoradiotherapy with the following schedules: docetaxel (DOC): 60mg / m2, ivgtt, D1 (03:30-04:30); Cisplatin (DDP): 60mg / m2, civ, d1-d5 (10:00-22:00); 5-fluorouracil (5-FU): 600mg / m2 / D 1, civ, d1-d5 (22:00-10:00); Synchronized DDP 100mg / m2, civ, D1 (10:00-22:00). Conventional group: Doc 60 mg / m2, ivgtt, D1; DDP 60mg/m2, ivgtt, d1; 5-FU 600mg/m2 /d 1, civ, d1-d5(120h); Synchronized DDP 100mg / m2, IVGTT, D1. Both groups were treated with IMRT at the same dose。 Lymphocyte and lymphocyte subsets were measured by flow cytometry before induction chemotherapy and 1 year versus 3 years after the end of concurrent chemoradiotherapy in patients, and changes in immune parameters, survival, and long-term toxicities were compared between the two groups. Results: One year after induction chemotherapy and concurrent chemoradiotherapy, the chronotherapy group showed higher plasma dendritic cells (PDC) than the conventional group (P &lt; 0.05). At 1 year after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD3-CD16 +, PDC, and MDC were significantly higher (P &lt; 0.05) in both pre - and post-treatment groups, and at 1 year after induction chemotherapy and concurrent chemoradiotherapy in the conventional group (P &lt; 0.05). At 3 years after induction chemotherapy and concurrent chemoradiotherapy, CD4 +, activated CD4 +, activated CD8 +, CD4 + CD25 +, cd3-cd19 +, and CD3-CD16 + were significantly increased in the chronic group (P &lt; 0.05), and CD4 +, activated CD4 +, activated CD8 +, and CD4 + CD25 + were significantly increased in the conventional group (P &lt; 0.05). In the comparison of toxic effects between the two groups, the incidences of xerostomia and dysphagia in the group at 3 years after treatment were significantly lower than those in the conventional group (P &lt; 0.05). There were no significant differences in PFS, OS, DMFS, LRRFS between the two groups at 3 years (P &gt; 0.05). Conclusions: Chronotherapy with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma more than conventional chemoradiotherapy reduces damage to dendritic cells and lymphocytes and alleviates toxic effects such as xerostomia and dysphagia at the same survival rate.

The Degree of Change and Relationship in Self-perceived Handicap and Acoustic Voice Quality Associated With Voice Therapy

Outcome measures describing acoustic voice quality and self-perceived vocal handicap are commonly used in clinical voice practice. Previous reports of the relationship between acoustic and self-perceived measures have found only limited associations, but it is unclear if acoustic measures associated with voice quality and self-perceived voice handicap change in a similar manner over the course of voice treatment. The current study, therefore, considered the relationship between the degree of change in Acoustic Voice Quality Index (AVQI) and Voice Handicap Index (VHI-30 and VHI-10) in dysphonic patients receiving treatment in a private practice voice clinic. Data were collected retrospectively from patient records of a private practice voice clinic over 80 consecutive months. For each patient, their voice disorder diagnosis, age, and biological sex were collected as well as pre-and post-treatment measures of the AVQI and VHI-30 or VHI-10 depending on which version was used. Correlations were calculated between the AVQI and VHI-30 and the AVQI and VHI-10 before and after treatment as well as for the percentage change of AVQI and VHI-30/VHI-10. Friedman and Kruskal-Wallis tests were used to determine the pre-and post-treatment effect and group differences respectively. Seventy-eight patients were included in the analyses. The scores of the AVQI (χ²[1]=24.01, P < 0.001), VHI-30 (χ²[1]=18.00, P < 0.001), and VHI-10 (χ²[1]=38.35, P < 0.001) all improved significantly after treatment. However, correlations between the AVQI and VHI-30, and the AVQI and VHI-10 were all non-significant, except for a moderate correlation between the AVQI and VHI-10 before treatment (r[43]=0.31, P = 0.04). The percentage change of the AVQI and the VHI-30/VHI-10 did not correlate significantly. Voice therapy significantly improved acoustic and self-perceived vocal outcome measures. However, there was no significant relationship between these measures before or after treatment, nor was there a relationship in their degree of change. Results support the notion that VHI and AVQI measure unique constructs and that voice therapy can have a positive impact on both.

Effect of trans-resveratrol on glutamate clearance and visual behaviour in rats with glutamate induced retinal injury

Glutamate-induced excitotoxic injury is widely described as a prominent pathophysiological mechanism in several neurodegenerative diseases including glaucoma. Glaucoma, the leading cause of irreversible blindness, is characterized by loss of retinal ganglion cells (RGC). Currently, the treatment focuses on lowering intraocular pressure (IOP) and no neuroprotective therapies are available. Since excessive glutamate-mediated neurotransmission underlies glaucomatous RGC apoptosis, enhancing synaptic glutamate clearance by glutamate transporters in glial cells is expected to protect against excitotoxic injury. Trans-resveratrol is known for its neuroprotective effects; however, its effects on the expression of glutamate transporters and glutamate clearance in retina remain unclear. Hence, in the current study, we investigated the protective effects of trans-resveratrol against glutamate-induced retinal injury in rats. Rats were intravitreally injected with glutamate alone or glutamate with trans-resveratrol as pre- and post-treatment. Animals were subjected to Open Field Test (OFT) on day six and a two-chamber mirror test on day seven post-injection. Subsequently, rats were sacrificed and retinal expression of excitatory amino acid transporter (EAAT)1 and EAAT2 gene and protein was determined using PCR and ELISA, respectively. Retinal glutamate concentration was measured using ELISA and retinal morphology was studied on H&E-stained retinal sections. It was observed that pre-treatment with trans-resveratrol causes gene expression for EAAT1 and EAAT2 to increase by 2.51 and 1.93 folds compared to glutamate-treated group (p < 0.001 and p < 0.01, respectively); while the same in trans-resveratrol post-treatment group showed a 1.58- and 1.44 folds upregulation (p < 0.05).The retinal EAAT1 and EAAT2 protein expression was significantly greater in trans-resveratrol pre-treatment group compared to glutamate-treated group (p < 0.05) but not in post-treatment group. Retinal glutamate concentration was1.64 folds greater in glutamate-treated group than the vehicle-treated group (p < 0.01) but the same was 1.27-fold lower in trans-resveratrol pre-treatment group compared to glutamate-treated group (p < 0.01). Corresponding to these findings, we observed preservation of retinal morphology and visual behaviour in trans-resveratrol pre-treatment group compared to glutamate-treated group. We did not observe similar effects of trans-resveratrol when it was given as post-treatment after glutamate administration. In conclusion, current study showed that pre-treatment with trans-resveratrol protects against glutamate induced changes in retinal morphology and visual behaviour by increasing the expression of EAAT1 and EAAT2 and increasing glutamate clearance in rat retinas. The results of this study may be relevant to disease conditions involving excitotoxic neuronal injury.