DN Group Research Articles

Histidine-trytophan-ketoglutarate cardioplegia reduces inflammatory response and serum levels of myocardial enzymes in newly developed right-thoracotomy rat model

The objective of this research was to establish a rat model for cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation that is both practical and economical and simulates clinical cardiac surgery. Concurrently, the study aimed to evaluate the myocardial protective effects conferred by histidine–tryptophan–ketoglutarate (HTK) cardioplegia. Thirty rats were randomly assigned to three groups: the histidine–tryptophan–ketoglutarate (HTK), 4:1 blood cardioplegia (BC) and del Nido cardioplegia (DN) groups. The cardiopulmonary bypass (CPB) procedure was implemented and sustained for a duration of one hour. Subsequent to the cessation of CPB, the rats were subjected to monitoring and observation for an additional two hours. Following this observation period, the heart and blood samples were procured for subsequent analysis. During CPB, the average hematocrit level was significantly below the typical physiological range (P < 0.001). Histopathological scores were notably lower in the HTK group in contrast to the BC group (P < 0.001) or the DN group (P < 0.001). At 2 h after weaning off CPB, the levels of CK and CKMB in the DN and BC groups were notably elevated compared to the HTK group (P < 0.001). The levels of IL-6 and TNF-α proteins were notably increased in all three groups (P < 0.001), with the BC and DN groups showing higher increases compared to the HTK group (P < 0.001). This compact animal model of cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation might allow for both the study of myocardial ischemia-reperfusion injury as well as cardioprotective strategies. HTK cardioplegia could reduce inflammatory response and serum levels of myocardial enzymes in this newly developed right thoracotomy rat model.

Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes.

Background: Diabetes, particularly type 2 diabetes (T2D), is linked with an increased risk of developing coronary heart disease (CHD). The present study aimed to evaluate potential circulating biomarkers of CHD by adopting a targeted proteomic approach based on proximity extension assays (PEA). Methods: The study was based on 30 patients with both T2D and CHD (group DC), 30 patients with T2D without CHD (group DN) and 29 patients without diabetes but with a diagnosis of CHD (group NC). Plasma samples were analyzed using PEA, with an Olink Target 96 cardiometabolic panel expressed as normalized protein expression (NPX) units. Results: Lysosomal Pro-X carboxypeptidase (PRCP), Liver carboxylesterase 1 (CES1), Complement C2 (C2), and Intercellular adhesion molecule 3 (ICAM3) were lower in the DC and NC groups compared with the DN groups. Lithostathine-1-alpha (REG1A) and Immunoglobulin lambda constant 2 (IGLC2) were found higher in the DC group compared to DN and NC groups. ROC analysis suggested a significant ability of the six proteins to distinguish among the three groups (whole model test p < 0.0001, AUC 0.83-0.88), with a satisfactory discriminating performance in terms of sensitivity (77-90%) and specificity (70-90%). A possible role of IGLC2, PRCP, and REG1A in indicating kidney impairment was found, with a sensitivity of 92% and specificity of 83%. Conclusions: The identified panel of six plasma proteins, using a targeted proteomic approach, provided evidence that these parameters could be considered in the chronic evolution of T2D and its complications.

Comparative analysis of Kinesio taping and dry-needling: effects on pain and disability in patients with mechanical low back pain

Background &amp; Objective: Low back pain (LBP) is an ever-increasing menace in the young men as well as women. Many factors causing it have been identified, the most common being improper spinal posture. LBP has been targeted by physicians, anesthetists, surgeons and rehabilitation medicine specialists. We compared the effects of Kinesio Taping and dry needling on pain reduction and disability improvement in patients diagnosed with mechanical chronic LBP. Method: A randomized control trial (RCT) was conducted at Rawal General and Dental Hospital and Al-Nafees hospital in Islamabad from January 2020 to October 2021. Probability-based sampling method was used to select participants for the study (simple random sampling). Thirty patients, aged 18 to 75 y were included. Sample size was calculated with Epitools. The selected patients were divided in two groups i.e., 15 patients in the Kinesio taping group (KT group) and 15 in the dry needling group (DN group). Two patients in the needling group were dropped. Numeric Pain Rating Scale (NPRS) and Roland-Morris Disability Index Questionnaire (RMDQ) were used to assess the pain and the disability at baseline, two weeks post-intervention and four weeks post-treatment. Chi-Square test was use to find association. Results: The mean age of the patients was 39.60 ± 13.69 y for KT group and 37.15 ± 12.54 y for DN group. The mean BMI for KT group was 27.15 ± 6.70 kg/m2 and for DN group 27.52 ± 5.13 kg/m2. Before treatment, there were no differences between the groups for NPRS and RMDQ. Both dry needling and Kinesio taping produced significant improvements in NPRS and RMDQ after two and four weeks of treatment (P &lt; 0.05). However, statistical analysis results showed that there was no association between pain and disability in patient with non-specific low back pain. (P &gt; 0.05). Conclusion: Both, Kinesio taping and dry needling, significantly reduced pain and disability after two- and four-weeks treatment in patients with low back pain, but there was no statistical differences between the pain and disability in both groups. Keywords: Disability; Dry Needling; Kinesio Tape; Low Back Pain; Numeric Pain Rating Scale; Physiotherapy Citation: Asad A, Irshad A, Hassan T, Kiran Q, Kouser S, Hassan F. Comparative analysis of Kinesio taping and dry-needling: effects on pain and disability in patients with mechanical low back pain. Anaesth. pain intensive care 2024;28(5):933−938; DOI: 10.35975/apic.v28i5.2561 Received: April 26, 2024; Reviewed: July 16, 2024; Accepted: July 18, 2024

Analgesic Effect of Dexmedetomidine-Nalbuphine Combination vs. Dexmedetomidine Alone in Donkeys Undergoing Field Castration under Total Intravenous Anesthesia.

This study evaluated the antinociceptive effect of dexmedetomidine-nalbuphine vs. dexmedetomidine alone in jacks undergoing field castration under total intravenous anesthesia. Jacks were premedicated with intravenous (IV) dexmedetomidine (5 µg/kg), either alone (Group D, n = 6) or in combination with 0.3 mg/kg nalbuphine (Group DN, n = 6). IV ketamine (1.5 mg/kg) and propofol (0.5 mg/kg) were used to induce general anesthesia, which was maintained by a continuous propofol (0.2 mg/kg/min) IV infusion. The quality of anesthesia, analgesia, and recovery were evaluated. A simple descriptive scale (SDS) was used to measure pain from the recovery time to 6 h later. The DN group exhibited improvements in analgesic and recovery quality and SDS of pain at 1-, 2-, and 3-h post-recovery. There was an apparent improvement in cardiac status, as evidenced by the enhanced heart rate and electrocardiogram findings compared to group D during surgery and recovery time. The DN group had a lower level of inflammatory cytokines, both during the surgery and shortly after recovery. Therefore, the dexmedetomidine-nalbuphine combination prior to IV anesthesia of ketamine and propofol in jacks undergoing field castration resulted in a stable surgical plane of anesthesia, improved antinociception, less pain postoperatively, and better cardiac stability.

Immature Surfactant Protein Type B and Surfactant Protein Type D Correlate with Coronary Heart Disease in Patients with Type 2 Diabetes.

Different specific surfactant proteins (SPs) have been associated with various pathological conditions, not only of the respiratory system, but also more recently with cardiovascular diseases, such as heart failure. The aim of the present study was to evaluate the role of SP-A, SP-D, and the precursor protein of SP-B (proSP-B) in the pathogenesis of cardiovascular damage in patients affected by type 2 diabetes (T2D). The study considered 31 patients with T2D (DN group), 34 patients with both T2D and coronary heart disease (CHD) (DC group), and 30 patients without diabetes but with a diagnosis of CHD (NC group). SP-A, SP-D, and proSP-B concentrations were determined in plasma samples, and were statistically compared using parametric and multivariate methods. Higher plasma concentrations of SP-D and proSP-B were found in patients affected by both T2D and CHD (DC group), and in patients with CHD without diabetes (NC group), in comparison to T2D patients (DN group). A significant correlation, both with linear regression (r = 0.3565, p = 0.001) and Principal Component Analysis (PCA), was found between the plasma levels of SP-D and proSP-B in the overall cohort of patients. No differences in SP-A were observed among the three groups of subjects. The present study extends the knowledge on the role of plasma SPs' levels as possible indicators of the risk of CHD being linked to T2D disease progression.

RUNX3-activated apelin signaling inhibits cell proliferation and fibrosis in diabetic nephropathy by regulation of the SIRT1/FOXO pathway

BackgroundDiabetic nephropathy is a major secondary cause of end-stage renal disease. Apelin plays an important role in the development of DN. Understanding the exact mechanism of Apelin can help expand the means of treating DN.MethodsMale C57BL/6 mice was used and STZ treatment was implemented for DN model establishment. Lentivirus systems including Lv-sh-RUNX3 and Lv-Apelin were obtained to knockdown RUNX3 and overexpress Apelin, respectively. A total of 36 mice were divided into 6 groups (n = 6 in each group): control, DN, DN + LV-Vector, DN + Lv-Apelin, DN + LV-Apelin + LV-sh-NC and DN + Lv-Apelin + Lv-sh-RUNX3 group. In vitro studies were performed using mesangial cells. Cell viability and proliferation was assessed through CCK8 and EDU analysis. Hematoxylin and eosin staining as well as Masson staining was implemented for histological evaluation. RT-qPCR was conducted for measuring relative mRNA levels, and protein expression was detected by western blotting. The interaction between SIRT1 and FOXO were verified by co-immunoprecipitations, and relations between RUNX3 and Apelin were demonstrated by dual luciferase report and chromatin immunoprecipitation.ResultsThe DN group exhibited significantly lower Apelin expression compared to control (p < 0.05). Apelin overexpression markedly improved blood glucose, renal function indicators, ameliorated renal fibrosis and reduced fibrotic factor expression (p < 0.05) in the DN group, accompanied by elevated sirt1 levels and diminished acetylated FOXO1/FOXO3a (p < 0.05). However, RUNX3 knockdown combined with Apelin overexpression abrogated these beneficial effects, leading to impaired renal function, exacerbated fibrosis, increased fibrotic factor expression and acetylated FOXO1/FOXO3a versus Apelin overexpression alone (p < 0.05). In mesangial cells under high glucose, Apelin overexpression significantly inhibited cell proliferation and fibrotic factor production (p < 0.05). Conversely, RUNX3 interference enhanced cell proliferation and the secretion of fibrotic factors. (p < 0.05). Remarkably, combining Apelin overexpression with RUNX3 interference reversed the proliferation and fibrosis induced by RUNX3 interference (p < 0.05). Mechanistic studies revealed RUNX3 binds to the Apelin promoter, with the 467–489 bp site1 as the primary binding region, and SIRT1 physically interacts with FOXO1 and FOXO3a in mesangial cells.ConclusionRUNX3 activated Apelin and regulated the SIRT1/FOXO signaling pathway, resulting in the suppressed cell proliferation and fibrosis in diabetic nephropathy. Apelin is a promising endogenous therapeutic target for anti-renal injury and anti-fibrosis in diabetic nephropathy. RUNX3 may serve as an endogenous intervention target for diseases related to Apelin deficiency.

Comparative study of choline alfoscerate as a combination therapy with donepezil: A mixed double-blind randomized controlled and open-label observation trial.

Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea. The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point. At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DA + DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DA + DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks. Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.

The genomic, transcriptomic, and immunological profile of patients with recurrent/refractory NSCLC.

8039 Background: Lung cancer is the leading cause of cancer-related deaths worldwide, and often presents at advanced stages, with &gt; 50% of patients presenting as stage III or IV. Patients with recurrent stage III NSCLC (R/R) previously treated with definitive chemoradiation and immunotherapy consolidation may have a difference in overall survival compared to de novo stage IV (DN). In this study, we aim to compare the molecular and immune landscapes of these two patient populations to identify potential genomic patterns and biomarkers of resistance. Methods: 3728 NSCLC specimens underwent sequencing of DNA (592-gene panel or whole exome) or RNA (whole transcriptome) or immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Patients were classified as R/R (n = 26) if they received Durvalumab and chemoradiation within 12 months (m) before tissue collection and treated with Pembrolizumab within 6 m after tissue collection. Patients treated with Pembrolizumab within 6 months after tissue collection and had no prior (or post) treatment with Durvalumab and chemoradiation at any point in time were classified as DN (n = 3702). Tumor microenvironment (TME) cell fractions were estimated from bulk RNA sequencing using QuanTIseq. Significance was determined using chi-square, Mann Whitney U and adjusted for multiple comparisons where applicable (q &lt; 0.05). Results: TP53 (91 vs 68%) and KEAP1 (30 vs. 14%, both p &lt; 0.05, q &gt; 0.05) mutation prevalence was higher in R/R, whereas a decreased prevalence of KRAS mutations was noted in this group (13 vs. 33%) as compared to the DN group. Compared to DN patients, R/R patients were associated with an increased prevalence of mutations in BCL2 (4.3 vs. 0%, q &lt; 0.05), BCL9 (4.3 vs. 0.2%, q &lt; 0.05), HNF1A (4.3 vs. 0.2%), TNFAIP3 (4.3 vs. 0.2%), AKT1 (4.3 vs. 0.4%), MAP3K1 (4.3 vs. 0.5%), and SPEN (4.3 vs. 0.6%; all p &lt; 0.05, q &gt; 0.05). Further, copy number amplification of NUTM1 (4.5 vs. 0%), SMO (4.3 vs. 0.5%), CHIC2 (4.5 vs. 0.2%; all q &lt; 0.05), PIK3CA (9 vs. 1.2%) and FLCN (4.5 vs. 0.3%; both p &lt; 0.05, q &gt; 0.05) was more common in R/R compared to DN. R/R TME was associated with decreased B cell (2.9 vs 4.4%, q &lt; 0.05) and regulatory T cell fractions (1.3 vs. 2.6%, p &lt; 0.05, q &gt; 0.05). Conclusions: R/R patient tumors had distinct molecular alterations and immune landscapes, including an increased prevalence of biomarkers associated with immunotherapy resistance ( TP53 and KEAP1 mutations) and lower tumor B- and T reg- cell fractions, which may suggest decreased likelihood of response to immunotherapy compared to patients with DN NSCLC. The RR population had a lower-than-expected percentage of KRASmutations. These distinct molecular differences highlight the need for NGS testing in the recurrent setting, despite initial NGS testing at diagnosis. Molecularly targeted interventions may be options in the future for patients with R/R Stage III NSCLC.

Comparison of remimazolam and desflurane in emergence agitation after general anesthesia for nasal surgery: a prospective randomized controlled study.

Remimazolam is an ultrashort-acting benzodiazepine. Few studies have evaluated the effects of remimazolam-based total intravenous anesthesia (TIVA) on emergence agitation (EA). This study aimed to compare the incidence and severity of EA between TIVA using remimazolam and desflurane. This prospective randomized controlled study enrolled 76 patients who underwent nasal surgery under general anesthesia. Patients were randomized into two groups of 38 each: desflurane-nitrous oxide (N2O) (DN) and remimazolam-remifentanil (RR) groups. The same protocol was used for each group from induction to emergence, except for the use of different anesthetics during maintenance of anesthesia according to the assigned group: desflurane and nitrous oxide for the DN group and remimazolam and remifentanil for the RR group. The incidence of EA as the primary outcome was evaluated using three scales: Ricker Sedation-Agitation Scale, Richmond Agitation-Sedation Scale, and Aono's four-point agitation scale. Additionally, hemodynamic changes during emergence and postoperative sense of suffocation were compared. The incidence of EA was significantly lower in the RR group than in the DN group in all three types of EA assessment scales (all P < 0.001). During emergence, the change in heart rate differed between the two groups (P = 0.002). The sense of suffocation was lower in the RR group than in the DN group (P = 0.027). RR reduced the incidence and severity of EA in patients undergoing nasal surgery under general anesthesia. In addition, RR was favorable for managing hemodynamics and postoperative sense of suffocation.

Neutrophil to lymphocyte ratio (NLR) as a surrogate marker of diabetic nephropathy

Background and objectives: Diabetic nephropathy and retinopathy are microvascular complications of diabetes. Nephropathy is clinically manifested as an increase in urine albumin excretion. Total white blood cell count is a crude but sensitive indicator of inflammation and studied in many cardiac and non-cardiac diseases as an inflammatory marker such as acute myocardial infarction, stroke, and heart failure. In this study, the association of neutrophil to lymphocyte ratio (NLR) with diabetic nephropathy and retinopathy. Methods: This was a prospective observational study performed on patients with diabetic nephropathy +/- retinopathy. A total of v104 subjects diagnosed with 3type 2 diabetes mellitus registered in this study. NLR was calculated by analyzing differential leukocyte count in complete blood picture. Spot Albuminuria was tested by immune turbidimetry method. Urine creatinine was tested by jaffe’s kinetic method by which spot urine microalbumin to creatinine ratio is calculated. ANOVA, Independent t-test, chi-square test, Karl Pearson correlation were applied to find significance. P&lt;0.05 was considered as statistically significant. Results: Totally 104 diabetic subjects were registered, 52 subjects had DN and 52 had normal urine albumin. Mean±SD NLR for a normal group is 2.5±1.1 and in DN group is 3.4±1.4 which was highly significant (P =0.001). Conclusion: Our study showed that there was a significant relation between NLR and DN; and positive correlation between NLR and urine microalbumin to creatinine ratio. Therefore, NLR may be considered as a novel surrogate marker of DN.

Short-term effect of frequency specific intramuscular electrical stimulation on post dry needling soreness of upper fibers of trapezius: A randomized controlled trial

ObjectivesThe purpose of this study was to compare the effect of frequency specific intramuscular electrical stimulation on post trigger point dry needling soreness. BackgroundDry needling (DN) with intramuscular electrical stimulation (DN/IMES) has been shown to be effective in reducing post needling soreness. The effect of frequency specific intramuscular electrical stimulation on post needling soreness has not been studied abundantly, but initial results are favorable. This study investigated the effect of frequency specific intramuscular electrical stimulation on post needling soreness. MethodsA convenience sample of 45 (α = 0.05, power = 95%) subjects was recruited for this study and randomly assigned to DN (n = 15), DN/IMES [f-2Hz] (n = 15) and DN/IMES [f-100Hz] (n = 15) groups. Pain Pressure Threshold (PPT) and Numeric Pain Rating Scale (NPRS) were measured before and 24 hours after the intervention. ResultBoth DN/IMES [f-2Hz and 100 Hz] groups showed statistically significant improvement in NPRS (p = 0.001 and 0.00005, respectively) and PPT (p = 0.004 and 0.0002, respectively). No statistically significant changes were observed in DN group in NPRS (p = 0.726) and PPT (p = 0.238). ConclusionBoth dry needling with Intramuscular electrical stimulation (DN/IMES [f-2Hz and 100Hz]) groups demonstrated statistically significant improvement in soreness as compared to DN group, but DN/IMES [f-100 Hz] group showed more significant improvement as compared to DN/IMES [f-2 Hz] group in reducing post needling soreness.

Relationship between the behavior change model and salt intake in hypertensive patients: a single non-specialized hypertension clinic prospective observational study.

We investigated whether changes in salt reduction readiness are associated with changes in estimated daily salt intake and blood pressure (BP). We divided 86 hypertensive patients into groups with high and low readiness for salt-reducing behavior [an up (UP) and a down (DN) groups, respectively] based on the transtheoretical model (TTM) over a 12-month observation period. We then investigated the relationships between changes in the TTM stage and changes in daily salt intake and BP over 12 months. The patients in the UP group had significantly increased urine potassium concentrations (from 51.2 ± 23.3 mEq/L at baseline to 56.9 ± 25.5 mEq/L at 12 months; P = 0.048) and significantly decreased estimated 24-h urinary salt excretion (from 9.7 ± 2.9 g/day at baseline to 8.4 ± 2.8 g/day at 12 months; P = 0.045). In addition, they also had significantly lower changes in urine sodium concentration (-13.1 ± 46.1 vs. -6.6 ± 59.7 mEq/L; P = 0.048), significantly increased changes in urine potassium concentration (5.7 ± 20.1 vs. -4.8 ± 28.6 mEq/L; P = 0.030), and significantly decreased changes in estimated 24-h urinary salt excretion (-1.3 ± 2.6 vs. -0.1 ± 2.6 g/day; P = 0.045) compared with patients in the DN group. However, their home BP did not improve over 12 months. The hypertensive patients who increased their readiness or maintained a high readiness for salt reduction over 12 months showed a significant increase in daily potassium intake and significant decrease in daily salt intake.

Dual Network Hydrogels Based on PRP and SA Promote the Retention Rate and Vascularization of Transplanted Fat.

Autologous adipose tissue often experiences ischemia and hypoxia after transplantation, leading to low retention rates and unstable operative impacts due to necrotic absorption. Platelet-rich plasma (PRP) can enhance fat regeneration and increase the fat retention rate after transplantation. However, the quick release of growth factors (GFs) in PRP decreases therapeutic efficiency. This study aimed to achieve a slow release of PRP to promote fat retention. We prepared a dual-network hydrogel (DN gel) based on FDA-approved PRP and sodium alginate (SA) through a simple "one-step" activation process. In vivo study, adipose tissue with saline (control group), SA gel (SA gel group), PRP gel (PRP gel group), and DN gel (DN gel group) was injected subcutaneously into the dorsum of nude mice. At 4 and 12 weeks after injection, tissues were assessed for volume and weight. Hematoxylin and eosin staining (HE) and immunofluorescence staining were performed for histological assessment. DN gel exhibits long-lasting growth factor effects, surpassing conventional clinical PRP gel regarding vascularization potential. In fat transplantation experiments, DN gel demonstrated improved vascularization of transplanted fat and increased retention rates, showing promise for clinical applications. DN gel-assisted lipofilling can significantly improve the retention rate and quality of transplanted fat. DN gel-assisted lipofilling, which is considered convenient, is a promising technique to improve neovascularization and fat survival. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

EFFECTS OF KINESIO-TAPING VS DRY NEEDLING IN THE MANAGEMENT OF MECHANICAL LOW BACK PAIN

Background of the study: Mechanical pain of musculoskeletal origin, known as nonspecific LBP (NSLBP), has symptoms that change depending on the type of physical activity [1]. About 85% of her LBP patients present in primary care settings are NSLBP patients. Methodology: Randomized control trial (RCT) conducted between between January 2020 and October, 2021, Rawal General and Dental Hospital and Al-Nafees, the hospital in Islamabad. Thirty patients were included in the study. Two participants were discontinued. There were two groups of patients i.e., 15 patients in the KT group and 13 patients in the DN group diagnosed of NSCLBP by orthopedic surgeon and referral to outpatient physiotherapy clinic. The Sample size was calculated using the OpenEpi scale. The Consent form was filled out by the participants before the initiation of the study. Pain Rating Scale, Roland-Morris Disability Index Questionnaire (RMDQ) and Global patient rating scale (PGR) were assessed at baseline, two weeks post-intervention and four weeks post-treatment. Results: Before treatment, there were no differences between the groups for PNRS, RMDQ and PGR. Both DN and KT produced significant improvements in all baseline measures (PNRS, RMDQ and PGR) after two weeks and four weeks of treatment (p&lt;0.05). Considerable improvements were observed in all variables in both groups after treatment. However, Statistical analysis ANOVA showed no significant differences in almost all measures between groups. (p&gt;0.05). Conclusion: Kinesio-taping is as effective as DN in managing back pain. When treating back pain, adding DN or KT to your exercise program can make a significant contribution to your treatment. Keywords: Dry needling, athletic tape, low back pain, disability evaluation, analogue pain scale, physical therapy specialty.

Complement activation products in tears of dry eye and meibomian gland dysfunction

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.

IL-33/ST2L signaling alleviates diabetic nephropathy by regulating endoplasmic reticulum stress and apoptosis

ObjectiveDiabetic nephropathy (DN) is a serious chronic complication of diabetes mellitus (DM). Endoplasmic reticulum (ER) stress is an important factor in the regulation of pathological processes in DN, and excessive ER stress can lead to apoptosis. Although the IL-33/ST2 axis is known to be involved in diabetic kidney disease or related nephropathy, its role and molecular mechanisms remain poorly understood in terms of DN. The purpose of this study was to investigate the effects of IL-33/ST2 signaling on DN and to characterize the roles that ER stress and apoptosis play in DN.MethodsTo investigate this study, mice were randomly assigned into DN (induced by 0.1% STZ) and Control groups. Biochemical indices (FBG, BUN, UPR, UCE) were measured in serum and urine samples to reflect blood glucose and kidney damage. Quantitative real-time PCR, western blot, and immunofluorescence were used to assess gene and protein expression of the IL-33/ST2 axis and ER stress relative signaling molecule. Apoptosis was analyzed by flow cytometry.ResultsIL-33 levels are significantly increased in the kidneys of patients and mice with DN. Double immunofluorescence staining showed that IL-33 colocalized with CD31-positive endothelial cells. Treatment with IL-33 attenuated kidney injury in Streptozotocin (STZ)-treated mice. In vitro, we showed that IL-33 attenuated ER stress and apoptosis in glomerular endothelial cells. However, sST2 treatment significantly reversed these effects of IL-33.ConclusionTogether, these data suggest that IL-33/ST2 signaling mitigates STZ-induced renal damage, partly at least, by suppressing ER stress and apoptosis. Therefore, IL-33 may be an effective therapeutic target in DN.

(5R)-5-hydroxytriptolide ameliorates diabetic kidney damage by inhibiting macrophage infiltration and its cross-talk with renal resident cells

ObjectiveDiabetic nephropathy (DN) is the main cause of end-stage renal disease, and there are no targeted treatment options at present. The efficacy of the new immunosuppressive drug (5R)-5-hydroxytriptolide (LLDT8) in improving kidney inflammation has been demonstrated in multiple studies. The present study was intended to investigate the preventive and therapeutic effects of LLDT8 on DN and to reveal its potential pharmacological mechanisms. MethodsThe effects of LLDT8 on liver and kidney functions, and urine microprotein of Streptozotocin (STZ) induced DN mice were detected. The protective effect of LLDT8 on the kidney tissue was observed by pathological staining and transmission electron microscopy. Cell culture experiments were performed to detect the effects of LLDT8 on the expression of chemokines and epithelial-mesenchymal transition (EMT) in high glucose-induced TCMK1 cells using real-time polymerase chain reaction (RT-PCR) and western blot (WB) techniques and to detect the influence of LLDT8 on the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. ResultsIn animal experiments, treatment with high-dose LLDT8 (0.25 mg/kg/2d) reduced 24 h urinary albumin excretion, improved structural kidney damage, and delayed fibrosis progression in DN mice. Immunofluorescence results showed that LLDT8 intervention reduced macrophage infiltration in kidney tissues of DN mice. PCR and WB results of kidney tissues showed reduced expressions of chemokines CCL2 and M-CSF1 in the LLDT8 intervention group compared to the DN group. In cellular assays, LLDT8 treatment reduced chemokine secretion in high glucose-induced TCMK1 cells, but had no effect on EMT of TCMK1 cells. LLDT8 treatment reduced the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells. ConclusionsThe present study suggests that LLDT8 could effectively inhibit the secretion of pro-inflammatory and pro-fibrotic factors by macrophages, which could alleviate high glucose-induced renal tissue injury and slow down the process of tissue fibrosis and DN.

Outcomes of Vdpace for Relapsed/Refractory Multiple Myeloma in the Era of Daratumumab Based Therapy

Background: Although the number of therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) has increased substantially, it still remains incurable and there remains a significant unmet need for treatment options for highly refractory patients. In this single-center real-world retrospective analysis, we evaluated the efficacy and safety of VDPACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) as a salvage therapy in the era of daratumumab. Methods: We retrospectively analyzed 88 patients with RRMM who received at least 1 cycle of VDPACE, between 1/2016 till 6/2023 at the University of Kansas Health System in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC). VDPACE consists of Bortezomib 1 mg/m2 subcutaneous on days 1, 4, 8 and, 11, doxorubicin 10 mg/m2 continuous infusion (CI) x 4 days, cisplatin 10 mg/m2 CI x 4 days, cyclophosphamide 400 mg/m2 CI x 4 days and etoposide 40 mg/m2 CI x 4 days. In this patient population, we identified two groups - 28 patients who were naïve to daratumumab (DN) and 60 patients who were refractory to daratumumab (DR). Descriptive analysis was performed on available data for patient characteristics, disease course and outcomes differentiating these two groups. Adverse events were graded based on the CTCAE v5.0 criteria. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. The Kaplan-Meier method was used for progression free survival (PFS) and overall survival (OS) assessment. Results: The median age for the entire patient population was 63 years (41-77). Median lines of therapies (LOT) in DN vs DR groups were 2 (1-10) vs 5 (1-10), respectively (Table 1). The ORR and ≥VGPR in DR vs DN was 53% vs 50% and 15% vs 29%, respectively. With a median follow-of 11.3 months (95% CI, 4.03-27), the median PFS for the entire patient population was 4 months (95% CI, 2.97-5.43) while the median OS was 11.1 months (95% CI, 6.97-14.9). However, the median OS for DN was 15.9 months (95% CI, 8.73-29.5) compared to 7.03 months ((95% CI, 6.27-13.57) p=0.06) for the DR group. See Figure 1. Treatment related toxicities were similar in both groups. The most common grade III/IV hematological toxicities were neutropenia (96% vs 93%, p=0.99), thrombocytopenia (93% vs 80% p=0.2), lymphopenia (89% vs 95%, p=0.3), and anemia (79% vs 73%, p=0.79). Transfusion of packed red blood cells (64% in DN vs 68% in DR group) and platelet (61% vs 80%) were common in both groups. Rates of neutropenic fever were similar in both groups; 46% in the DN vs 35% in the DR group, p=0.62, with pneumonia being the most common infection seen in 11% vs 5% of the patients, respectively. Sixty-day Rehospitalization rates in the two groups were 21% vs 50%. There was no treatment-related mortality reported with this regimen. The difference in OS after VD-PACE in DR and DN patients could be explained by higher no of prior LOT, presence of high risk cytogenetics, double refractory status, and limited options available for salvage. Conclusions: Our study shows that while the response rates with VDPACE were comparable in the two groups, there was a higher median OS in the DN. Hematologic adverse events were common in both groups, but the rate of re-hospitalization was higher in the DR group. Based on these results, VDPACE remains a safe and effective salvage therapy for patients with RRMM. For DR patients receiving VD-PACE, strong consideration should be given to clinical trials given poor long-term outcomes.

Lesion-aware attention network for diabetic nephropathy diagnosis with optical coherence tomography images.

For early screening of diabetic nephropathy patients, we propose a deep learning algorithm to screen high-risk patients with diabetic nephropathy from retinal images of diabetic patients. We propose the use of attentional mechanisms to improve the model's focus on lesion-prone regions of retinal OCT images. First, the data is trained using the base network and the Grad-CAM algorithm locates image regions that have a large impact on the model output and generates a rough mask localization map. The mask is used as a auxiliary region to realize the auxiliary attention module. We then inserted the region-guided attention module into the baseline model and trained the CNN model to guide the model to better focus on relevant lesion features. The proposed model improves the recognition of the lesion region. To evaluate the lesion-aware attention network, we trained and tested it using OCT volumetric data collected from 66 patients with diabetic retinal microangiopathy (89 eyes, male = 43, female = 23). There were 45 patients (60 eyes, male=27, female = 18) in DR group and 21 patients (29 eyes, male = 16, female = 5) in DN group. Our proposed model performs even better in disease classification, specifically, the accuracy of the proposed model was 91.68%, the sensitivity was 89.99%, and the specificity was 92.18%. The proposed lesion-aware attention model can provide reliable screening of high-risk patients with diabetic nephropathy.

Presence of Non-Diabetic Kidney Diseases in Biopsy Specimens of Diabetic Patients' Single Center Experience.

The complications of type 2 diabetes mellitus (T2DM) are well known and one of them is diabetic chronic kidney disease (DCKD). Over time, it has become clear that patients with T2DM can have nondiabetic chronic kidney diseases (NDCKD), especially those that affect the glomeruli. Clinical indicators for identifying DCKD from NDCKD with high sensitivity and specificity have not yet been identified. Therefore, kidney biopsy remains the golden standard for DCKD diagnosis in patients with T2DM. Despite some indications for kidney biopsy, criteria for a biopsy differ between countries, regions, and doctors. The aim of the study was to analyze the biopsy findings in our T2DM population and the justification of the biopsy according to widely accepted criteria. This single center retrospective study analyzed data from 74 patients with T2DM who underwent kidney biopsy from January 2014 to January 2021. According to the biopsy data, we categorized31 patients in the DN group, patients with typical diabetic glomerulopathy, 11 patients in the mixed group, patients who had pathohistological elements for both DN and non-DN glomerulopathy, and 32 patients in the non-DN group, patients with primary glomerulopathy not linked with DM. In the non-DN and mixed groups, the most frequent glomerulopathy was mesangioproliferative glomerulonephritis, including IgA and non-IgA forms, found in 10 patients, and membranous nephropathy (MN) in 10 patients. We analyzed several parameters and only the amount of proteinuria was found to be significantly linked to biopsy findings related to DN. With the existing criteria for kidney biopsy, we managed to detect changes in the kidneys in about half of our patients with T2DM. These patients required specific treatment, different from that which we use for DCKD patients.