Cycle Threshold Values as Indication of Increasing SARS-CoV-2 New Variants, England, 2020-2022.

Early detection of increased infections or new variants of SARS-CoV-2 is critical for public health response. To determine whether cycle threshold (Ct) data from PCR tests for SARS-CoV-2 could serve as an early indicator of epidemic growth, we analyzed daily mean Ct values in England, UK, by gene target and used iterative sequential regression to detect break points in mean Ct values (and positive test counts). To monitor the epidemic in England, we continued those analyses in real time. During September 2020-January 2022, a total of 7,611,153 positive SARS-CoV-2 PCR test results with Ct data were reported. Spike (S) gene target (S+/S-)-specific mean Ct values decreased 6-29 days before positive test counts increased, and S-gene Ct values provided early indication of increasing new variants (Delta and Omicron). Our approach was beneficial in the context of the first waves of the COVID-19 pandemic and can be used to support future infectious disease monitoring.

Effect of different squatting exercises on menstrual aspects, pelvic mechanics and uterine circulation in primary dysmenorrhoea: a randomised controlled trial.

This was a randomised trial aimed to determine squatting exercises' effects on menstruation, pelvic mechanics, and uterine circulation in primary dysmenorrhoea. A total of 120 females with primary dysmenorrhoea were assigned into group (A), receiving yoga protocol, or groups (B, C & D), receiving yoga protocol added to modified wall squat, sumo squat, or deep squat, respectively. Menstrual pain and distress, pelvic inclination, and uterine circulation were measured before and after interventions using a pain scale, a questionnaire, palpation metre, and Doppler ultrasonography, respectively. There was a significant reduction in pain intensity in groups B & C (effect size = 3.97 & 5.89, respectively), compared to group A (effect size = 3.68), and in group C (effect size = 5.89) compared to group D (effect size = 3.94), pain subscale in the groups B, C & D (effect size = 1.69, 3.3 & 3.41, respectively), compared to group A (effect size= 2.47), water retention subscale in group D effect size 0.90 compared to group A (effect size =0.41) and in the questionnaire total scores in the groups C &D (effect size = 2.3 & 2.46, respectively) when compared to group A (effect size =1.94). Adding squatting exercises to yoga is more effective than yoga alone in reducing menstrual pain and distress.IMPACT STATEMENTWhat is already known on this subject? Physical exercises positively affect primary dysmenorrhoea in terms of decreased pain and distress, possibly through altering faulty posture. Squatting exercises affect lumbopelvic mechanics.What do the results of this study add? This study explores the effect of squatting exercises on pelvic inclination, menstrual aspects, and circulation.What are the implications of these findings for clinical practice and/or further research? Squatting exercises can be utilised to affect pelvic mechanics leading to decreased menstrual pain and distress, because of decreased pelvic congestion.

Effect of aerobic exercises versus laser acupuncture in treatment of postmenopausal hot flushes: a randomized controlled trial.

[Purpose] To compare the effect of aerobic exercises versus laser acupuncture in treatment of postmenopausal hot flushes. [Subjects and Methods] This study was designed as single blind randomized controlled trial. A total of 48 postmenopausal women complained of hot flushes. Their ages ranged between 45 to 55 years and were randomly assigned into 2 equal groups: group (A), which received an aerobic exercises, and group (B), which received laser acupuncture. Both groups recieved 3 sessions per week for two months. The level of follicular stimulating hormone, lutelizing hormone, and hot flushes dairy card were assessed the severity of hot flahes before and after treatment program. [Results] There were Significant reduction in FSH, LH, and menopausal daily hot flush scale in group A compared with group B at the post treatment. [Conclusion] Eight week program of an aerobic exercises yields improvement in FSH, LH, and decrease in severity of hot flushes assessed by hot flush dairy card than laser acupuncture in the treatment of postmenopausal hot flashes.

Efficacy of exercise on pelvic pain and posture associated with endometriosis: within subject design.

[Purpose] This study was carried out to determine the effect of an exercise program on pelvic pain and posture associated with endometriosis. [Subjects and Methods] This study was designed as repeated measures design that compared one group of 20 patients (age range 26-32 years) diagnosed by laparoscope as having mild or moderate endometriosis before, after 4 weeks, and after 8 weeks of exercise program. The exercise program parameters were based on the American College of Obstetricians and Gynecologists guidelines for exercise suitable for sedentary women. To assess the intensity of endometriosis pain, a present pain intensity scale was used. On the other hand, a raster stereography system was used to assess the posture. [Results] After 8 weeks of performing the exercise regimen, there was a statistically significant decrease in the patients' pain intensity and thoracic kyphosis angle program in compared with pre treatment. [Conclusion] Ultimately it was proven that eight weeks of an exercise program is very effective in decreasing pain and postural abnormalities associated with endometriosis.

Effect of aquatic versus land based exercise programs on physical performance in severely burned patients: a randomized controlled trial.

[Purpose] To compare the effect of an aquatic-based versus a land-based exercise regimen on the physical performance of severely burned patients. [Subjects and Methods] Forty patients suffering from severe burn (total body surface area more than 30%) were recruited from several outpatient clinics in Greater Cairo. Their ages ranged between 20 to 40 years and were randomly assigned into two equal groups: group (A), which received an aquatic based exercise program, and group (B), which received a land-based exercise program. The exercise program, which took place in 12 consecutive weeks, consisted of flexibility, endurance, and lower and upper body training. Physical performance was assessed using 30 seconds chair stand test, stair climb test, 30 meter fast paced walk test, time up and go test, 6-minute walk test and a VO2max evaluation. [Results] Significantly increase in the 30 second chair stand, 6-minute walk, 30 meter fast paced walk, stair climb, and VO2 max tests and significantly decrease in the time up and go test in group A (aquatic based exercise) compared with group B (a land-based exercise) at the post treatment. [Conclusion] Twelve-week program of an aquatic program yields improvement in both physical performance and VO2 max in patients with severe burns.

Effect of backpack shoulder straps length on cervical posture and upper trapezius pressure pain threshold.

[Purpose] This study was performed to investigate the effect of the length of backpack shoulder straps on upper trapezius muscle pain threshold and craniovertebral angle. [Subjects and Methods] There were 25 participants, with ages from 15 to 23 years old. Upper trapezius pain threshold and craniovertebral angle were measured for all subjects without the backpack then re-measured after walking on a treadmill for 15 min under 2 conditions: 1) wearing a backpack with short straps; and 2) wearing a backpack with long straps. [Results] there was a significant reduction in upper trapezius pain threshold and craniovertebral angle while carrying a backpack with long shoulder straps, compared to use of a backpack with short shoulder straps or no backpack. [Conclusion] A backpack with short straps is less harmful than a backpack with long straps. This result should be considered in ergonomic design of backpacks to reduce the incidence of various physiological and biomechanical disorders.

Investigating dynamics, etiology, pathology, and therapeutic interventions of Caligus clemensi and Vibrio alginolyticus co-infection in farmed marine fish.

This study investigated a disease outbreak characterized by caligid copepod infestations and subsequent secondary bacterial infections in European seabass (Dicentrarchus labrax) and flathead grey mullet (Mugil cephalus) cultivated at a private facility in the Deeba Triangle region of Egypt. Moribund fish displayed brown spots on the skin, tongue, and gills, along with lethargy and excess mucus. The fish suffered severe infections, exhibiting external hemorrhages, ulcers, and ascites. The fish had pale, enlarged livers with hemorrhaging. Comprehensive parasitological, bacteriological, molecular, immunity and histopathological analyses were conducted to identify the etiological agents and pathological changes. Caligid copepod infestation was observed in wet mounts from the buccal and branchial cavities of all examined fish, and the caligids were identified as Caligus clemensi through COI gene sequencing and phylogenetic analysis. Vibrio alginolyticus was confirmed as a secondary bacterial infection through biochemical tests, recA gene sequencing, and phylogenetic analyses. Antibiotic susceptibility testing revealed resistance to ß-lactams, aminoglycosides, and trimethoprim-sulfamethoxazole in V. alginolyticus isolates. Upregulation of the inflammatory marker IL-1ß in gill and skin tissues indicated a robust cell-mediated immune response against the pathogens. Histopathological examination revealed severe tissue damage, hyperplasia, hemorrhage, and congestion in the gills, along with hepatocellular degeneration and steatosis in the liver, providing initial insights into this outbreak. A comprehensive therapeutic regimen was implemented, comprising prolonged hydrogen peroxide immersion baths, followed by the application of the nature-identical plant-based compound Lice-less and probiotic Sanolife Pro-W supplementation. This integrated approach effectively eliminated C. clemensi infestations, controlled secondary bacterial infections, and restored fish health, reducing morbidity and mortality rates to minimal levels.

Is muscle activation diverse in females with isolated patellofemoral osteoarthritis contrasted with age-matched healthy controls during stair descent task?

Background: Patellofemoral osteoarthritis (PF OA) is exceptionally predominant and limiting. However, little is known about the risk factors that contribute to its onset and progression. Purpose: The aim of this study was to decide if women with PF OA descend stairs using different muscular activation strategies compared to similarly aged healthy controls. Methods: Thirty-one women with isolated PF OA and 11 similarly aged healthy women took part in this study. The activation onset and duration of PF OA in vastus medialis oblique (VMO), vastus lateralis (VL), gluteus medius (GM), transversus abdominis (TrA), and multifidus muscles were evaluated during the stair descent task using surface electromyography (EMG). Results: There was a non-significant difference between women with PF OA and healthy controls regarding all tested variables, except for the GM activation onset that was significantly delayed in women with PF OA, with the p-value of 0.011. Conclusion: The causes of PF OA differ and might not always be due to a lack of quadriceps strength or VMO activation deficiency, and prospective longitudinal studies are required to confirm this assumption.

2-methoxyestradiol sensitizes tamoxifen-resistant MCF-7 breast cancer cells via downregulating HIF-1α.

The clinical studies for breast cancer (BC) are now assessing the efficacy of 2-Methoxyestradiol (2-ME), a naturally occurring derivative of estradiol. Our study aimed to explore the potential of combining the 2-ME and tamoxifen (TAM) on sensitization of TAM-resistant cells using LCC2 the TAM-resistant cells as a model and comparing the results to the sensitive cells MCF-7. Sulphorhodamine-B (SRB) assay is used to examine the 2-ME chemo-sensitizing impact on the cytotoxicity of TAM on LCC2 cells. Colorimetric assay kits were used to assess the level of the apoptosis-related markers caspases 3, Bcl2, and Bax in cell lysate. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was measured using western blotting. Total cholesterol and triglyceride (TG) levels were examined colorimetrically, using the BIOLABO kit. The use of 2-ME enhanced the cytotoxic effects of TAM and effectively reversed TAM resistance. This was achieved by inhibiting the expression of HIF-1α, while concurrently increasing the levels of apoptotic marker caspase-3, as well as the pro-apoptotic protein Bax. Additionally, there was a reduction in the levels of Bcl2, an anti-apoptotic protein. Furthermore, a reduction in TG and cholesterol levels was noted. Our findings show that HIF-1α plays an important role in TAM resistance and that suppression of HIF-1α by 2-ME-mediated sensitization of BC-resistant cells to TAM. Therefore, the concurrent administration of TAM/2-ME might potentially serve as a viable therapeutic approach to address TAM resistance and enhance the overall therapy efficacy for patients with BC.

Comparing Minimally Invasive Percutaneous Plate Osteosynthesis With Interlocking Intramedullary Nail Fixation for the Management of Adult Extra-Articular Distal Tibial Fractures: A Comprehensive Systematic Review and Meta-Analysis.

Intramedullary nailing (IMN) and minimally invasive percutaneous plate osteosynthesis (MIPPO) fixation are both viable approaches for managing distal tibia fractures. IM nailing offers advantages in terms of shorter operation time, faster union, and reduced infection rates, yet it may lead to alignment issues and residual knee pain. Conversely, MIPPO fixation provides better alignment and minimizes knee discomfort but comes with a higher risk of soft-tissue complications and hardware irritation. Notably, this review reveals that MIPPO is associated with a greater risk of both superficial (15% vs. 7% for IMN) and deep infections (14% vs. 6.3% for IMN). This study aims to comprehensively assess the optimal surgical approaches for distal tibia fractures by comparing clinical and functional outcomes between MIPPO and interlocking IMN techniques in treating extra-articular distal tibial fractures. Key outcome parameters include operation duration, union time, non-union occurrence, malunion cases, infection rates, secondary surgical interventions, and functional results, as indicated by quality of life and ankle scores. Regarding union complications, it is notable that IMN demonstrates a higher incidence of malunion, affecting 14.7% of patients compared to 8.8% in the MIPPO fixation group. Interestingly, both treatment methods exhibit a similar incidence of non-union, occurring in 3.5% of patients in both groups. Furthermore, when assessing the union time, IMN fixation notably achieves significantly shorter union times, especially evident in AO 43A fracture types and closed fractures. The mean time for union is 18 weeks with IMN compared to 20 weeks with MIPPO fixation. In our analysis of nine studies involving 813 patients, the reported operation times revealed an overall weighted mean operation time of 74.1 minutes (ranging from 56.4 to 124 minutes) for IMN and 85.4 minutes (ranging from 51.4 to 124 minutes) for MIPPO fixation. Notably, the operation time for IMN was significantly shorter compared to MIPPO, showing a weighted mean difference (WMD) of -11.24 minutes, with a 95% confidence interval (CI) ranging from -15.44 to -7.05 (P<0.05). This difference exhibited significant moderate heterogeneity (I2 = 68%). In light of this comprehensive study, both MIPPO and IMN emerge as equally effective therapeutic options for addressing functional outcomes in distal tibial extra-articular fractures. While IMN offers several advantages, including lower infection rates, reduced implant irritation, shorter operation time, and earlier weight-bearing and union, it is associated with a heightened risk of malunion and anterior knee pain. Consequently, the choice of implant should be tailored on a case-by-case basis. Patients at elevated infection risk, stemming from factors, such as advanced age, comorbidities, smoking, or severe soft tissue injuries, are better suited for nail treatment. Conversely, MIPPO fixation may present a more advantageous choice for young, active, and healthy patients, given its ability to mitigate the risk of knee pain and malunion.

Virtual reality versus Biodex training in adolescents with chronic ankle instability: a randomized controlled trial.

Introduction: Ankle instability is a common injury in athletes, affecting the quality of life, functional limitation, as well as static and dynamic balance. The aim of the study was to compare the efficacy of virtual reality and Biodex balance training in the treatment of ankle instability in adolescent athletes. Material and methods: Ninety football players were enrolled in this study after the assessment of their eligibility. Their age ranged from 12 to 16 years. They were randomly allocated to three groups of equal numbers. Group 1 received a guideline protocol, group 2 received the same guideline protocol in addition to Wii Sport Training, and group 3 received the same guideline protocol in addition to Biodex balance training. All groups received treatment protocols three times a week for 3 months. Outcome measures included the stability indices (overall stability, anteroposterior stability, and mediolateral) measured by the Biodex Balance System as well as ankle instability measured by the Cumberland Ankle Instability Tool. Measurements were collected at the baseline and after 3 months of treatment. Results: Post-treatment findings revealed a statistically significant decrease in the overall, anteroposterior, and mediolateral stability indices, as well as significant increase in Cumberland Ankle Instability outcomes of all groups (p < 0.05). On the other hand, there were no statistically significant differences between the virtual reality and Biodex balance training groups. Conclusions: Virtual reality training has a significant effect which appears to be similar to the Biodex balance training in adolescent athletes with chronic ankle instability.

Clinical and histopathological responses to bee venom phonophoresis in treating venous and diabetic ulcers: a single-blind randomized controlled trial.

Introduction: Chronic venous and diabetic ulcers are hard to treat that cause patients long time of suffering as well as significant healthcare and financial costs. Purpose: The conducted study was to evaluate the efficacy of bee venom (BV) phonophoresis on the healing of chronic unhealed venous and/or diabetic foot ulcers Also, to compare the healing rate of diabetic and venous ulcers. Methodology: The study included 100 patients (71 males and 29 females) with an age range of 40-60 years' old who had chronic unhealed venous leg ulcers of grade I, grade II, or diabetic foot ulcers with type II diabetes mellitus. They randomly assigned into four equal groups of 25: Group A (diabetic foot ulcer study group) and group C (venous ulcer study group) who both received conservative treatment of medical ulcer care and phonophoresis with BV gel, in addition to group B (diabetic foot ulcer control group) and group D (venous ulcer control group) who both received conservative treatment of medical ulcer care and received ultrasound sessions only without BV gel. Wound surface area (WSA) and ulcer volume measurement (UVM) were used to assess the ulcer healing pre-application (P0), post-6 weeks of treatment (P1), and after 12 weeks of treatment (P2). In addition to Ki-67 immunohistochemistry was used to evaluate the cell proliferative in the granulation tissue of ulcers pre-application (P0) and after 12 weeks of treatment (P2) for all groups. Results: This research revealed a statistical significance improvement (p ≤ 0.0) in the WSA, and UVM with no significant difference between study groups after treatment. Regarding Ki-67 immunohistochemistry showed higher post treatment values in the venous ulcer group in comparison to the diabetic foot ulcer group. Conclusion: Bee venom (BV) provided by phonophoresis is effective adjuvant treatment in accelerating venous and diabetic foot ulcer healing with higher proliferative effect on venous ulcer. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05285930.

miRNAs as potential game-changers in head and neck cancer: Future clinical and medicinal uses.

Head and neck cancers (HNCs) are a group of heterogeneous tumors formed most frequently from epithelial cells of the larynx, lips, oropharynx, nasopharynx, and mouth. Numerous epigenetic components, including miRNAs, have been demonstrated to have an impact on HNCs characteristics like progression, angiogenesis, initiation, and resistance to therapeutic interventions. The miRNAs may control the production of numerous genes linked to HNCs pathogenesis. The roles that miRNAs play in angiogenesis, invasion, metastasis, cell cycle, proliferation, and apoptosis are responsible for this impact. The miRNAs also have an impact on crucial HNCs-related mechanistic networks like the WNT/ß-catenin signaling, PTEN/Akt/mTOR pathway, TGFß, and KRAS mutations. miRNAs may affect how the HNCs respond to treatments like radiation and chemotherapy in addition to pathophysiology. This review aims to demonstrate the relationship between miRNAs and HNCs with a particular emphasis on how miRNAs impact HNCs signaling networks.

Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats.

AIM: this study aims to explore the effect of androgen receptor (AR) blockade by flutamide on some renal pathologic changes such as inflammation, apoptosis, and fibrosis in male rats. MAIN METHODS: Firstly, we investigated the potential effect of AR blockade on renal inflammatory intermediates including IL-1ß, IL-6, TNF-α, NF-Òšß proteins, and the renal gene expression of NF-Қß. Besides inflammation, we also assessed the apoptosis pathways including the caspases 3 & 9, mTOR, pAKT proteins, and BAX gene expression. Besides inflammation and apoptosis pathways, we also investigated the effect of androgen blockade on renal fibrosis intermediates including vimentin, TGFß-1, α-SMA, MMP-9, collagen type-III, collagen type-IV, and the renal expression of the col1A1 gene. Besides previous pathological pathways, we assessed the expression of chloride channel protein-5 (ClC-5), as an important regulator of many renal pathological changes. Finally, we assessed the impact of previous pathological changes on renal function at biochemical and pathological levels. KEY FINDINGS: We found that AR blockade by flutamide was associated with the down-regulation of renal inflammation, apoptosis, and fibrosis markers. It was associated with expression down-regulation of IL-1ß & IL-6, TNF-α, NF-Қß, caspases 3 & 9, mTOR, MMP-9, collagens, TGFß-1, and α-SMA. Away from down-regulation, we also found that AR blockade has upregulated ClC-5 and pAKT proteins. SIGNIFICANCE: AR is a major player in androgens-induced nephrotoxicity. AR blockade downregulates renal fibrosis, inflammation, and apoptosis pathways. It may be helpful as a strategy for alleviation of renal side effects associated with some drugs. However; this needs further investigations.

Design and Utilization of a Direct Methanol Fuel Cell.

This study introduces a step-by-step, summarized overview of direct methanol fuel cell (DMFC) fundamentals, thermodynamic-electrochemical principles, and system evaluation factors. In addition, a parametric investigation of a JENNY 600S DMFC is conducted to simulate cell performance behavior under varying operating conditions. The system is mathematically modeled and solved in MATLAB and accounts for multi-irreversibilities such as the activation and ohmic and concentration overpotentials. The performance of the modeled system was validated against theoretical and experimental results from the literature. The results indicated that increasing the fuel cell's operating temperature yields enhanced output cell voltages due to enhanced methanol oxidation reactions. Nevertheless, the maximum efficiency limits of the fuel cell tend to decrease with an increase in temperature. In addition, the model has also depicted that enhanced output cell voltages are associated with increased oxygen consumption, resulting in the lower exit flowrates of the reactants.

miRNA-193b-5p Suppresses Pancreatic Cancer Cell Proliferation, Invasion, Epithelial Mesenchymal Transition, and Tumor Growth by Inhibiting eEF2K.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths in the US due to the lack of effective targeted therapeutics and extremely poor prognosis. OBJECTIVE: The study aims to investigate the role of miR-193b and related signaling mechanisms in PDAC cell proliferation, invasion, and tumor growth. METHODS: Using PDAC cell lines, we performed cell viability, colony formation, in vitro wound healing, and matrigel invasion assays following transfection with miR-193b mimic or control-miR. To identify potential downstream targets of miR-193b, we utilized miRNA-target prediction algorithms and investigated the regulation of eukaryotic elongation factor-2 kinase (eEF2K) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways and mediators of epithelial mesenchymal transition (EMT). The role of miR-193b in PDAC tumorigenesis was evaluated in in vivo tumor growth of Panc-1 xenograft model in nude mice. RESULTS: We found that miR-193b is under expressed in PDAC cells compared to corresponding normal pancreatic epithelial cells and demonstrated that ectopic expression of miR-193b reduced cell proliferation, migration, invasion, and EMT through downregulation of eEF2K signaling in PDAC cells. miR-193b expression led to increased expression of E-Cadherin and Claudin-1 while decreasing Snail and TCF8/ZEB1 expressions via eEF2K and MAPK/ERK axis. In vivo systemic injection of miR-193b using lipid-nanoparticles twice a week reduced tumor growth of Panc-1 xenografts and eEF2K expression in nude mice. CONCLUSIONS: Our findings suggest that miR-193b expression suppresses PDAC cell proliferation, migration, invasion, and EMT through inhibition of eEF2K/MAPK-ERK oncogenic axis and that miR-193b-based RNA therapy might be an effective therapeutic strategy to control the growth of PDAC.

Distal hypospadias repair: Comparative study between snodgrass and transverse preputial onlay flap.

INTRODUCTION: Distal hypospadias repair has several operative strategies such as tubularized incised plate (TIP); Transverse preputial onlay flap (TPOF) and Modified Mathieu Procedure. The aim of our work is to compare between TIP and TPOF techniques in the outcome. MATERIAL AND METHOD: We conducted this comparative study on 66 patients with different types of distal hypospadias divided in two groups A and B for TIP and TPOF respectively. We reported outcome and complications for both TIP and TPOF repair. Our results revealed mean operative time was significantly higher in group B (123.1 ± 6.8 min) than in group A (93.73 ± 3.9 min, P value < 0.001). Postoperative urinary fistula was reported in group A (15.2%) while no fistula in group B (p value = 0.05). The vertical slit appearance of meatus was better in group A (54.5%) than in group B (24.2%, P value 0.023). As regard to hypospadias objective scoring evaluation (HOSE) (Summary Figure) the meatal shape score was higher in group A (1.55 ± 0.51) than in group B (1.24 ± 0.44, p value = 0.0 l), the urinary stream score was significantly higher in group A (1.82 ± 0.39) than in group B (1.97 ± 0.17, p value = 0.04) and the urinary fistula score was significantly higher in group A (3.79 ± 0.60) than in group B (4 ± 0, p value = 0.04). DISCUSSION: Complications are more common after TIP than in TPOF. As regard the meatus shape, the naturally looking vertical slit like meatus was achieved more in the TIP than in TPOF. We advocate further studies with a large number of patients with a long follow up period. CONCLUSION: TPOF is a great option to consider in cases of distal hypospadias because it is an effective technique for primary distal hypospadias repair with a good cosmetic outcome and a low associated complication.

Effect of High-Power Laser Therapy Versus Shock Wave Therapy on Pain and Function in Knee Osteoarthritis Patients: A Randomized Controlled Trial.

Objective: The aim of this study was to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and high-intensity laser therapy (HILT), as outpatient physical therapy modalities, on knee osteoarthritis (KOA) patients. Materials and methods: The treatment program was completed by 40 individuals with stage II KOA (according to Kellgren and Lawrence) who were randomly allocated to one of two groups. They have had more than grade 3 pain on the visual analog scale (VAS) during activities for the last 3 months, with body-mass index less than 30 and no history of knee operation, fracture, cancer, or other neuromuscular or musculoskeletal diseases that may affect study results. The ESWT group (n = 20, mean age = 40.12 ± 9.45 years) received ESWT, 0.05 mJ/mm2, one session/week for 4 weeks, and the HILT group (n = 20, mean age = 46.62 ± 8.68 years) received HILT, 1500 mJ/cm2 in each session, three sessions/week for 4 weeks. Both groups received conservative physical therapy programs. Before and after 4 weeks of intervention, pain, physical function, and disability were assessed using a VAS, 6-min walking test, and the Western Ontario and McMaster Universities Osteoarthritis Index. Results: When the pre- and post-treatment mean values of dependent variables of both groups were compared, there were statistically significant improvements in both groups. Significant differences in the measured variables were also discovered in favor of the HILT group compared with the ESWT group. Conclusions: HILT showed a superior effect compared with ESWT on pain, physical function, and disability in chronic KOA patients. Pan African Clinical Trials Registry number: PACTR202007638955907.

Hydroxycitric acid reverses tamoxifen resistance through inhibition of ATP citrate lyase.

Lipid metabolic reprogramming is involved in mediating tamoxifen (TAM) response in breast cancer cells. Published microarray data indicated that ATP citrate lyase (ACLY) is overexpressed in TAM-resistant BC cells. Hydroxycitric acid (HCA) is a powerful competitive inhibitor of the enzyme ACLY, which links carbohydrates and lipids metabolism. However, whether inhibition of ACLY could modulate TAM response in TAM-resistant BC cells remained unexplored. Thus the current study aimed to explore the effect of ACLY inhibition on TAM-resistant BC cells. The cytotoxicity of TAM and/or HCA on LCC2 and its TAM-sensitive counterpart MCF7 cells was evaluated. Also, the effect of TAM and/or HCA treatments on ACLY protein levels were investigated by western blotting. In addition, the effects of TAM and/or HCA on caspase-3, Bax, and Bcl2 levels were evaluated by ELISA.; besides, and flow cytometric analysis was performed for the detection of apoptosis. Moreover, cholesterol and triglyceride contents of LCC2 and MCF7 were quantified colorimetrically. Our results demonstrated that TAM/HCA co-treatment synergistically diminished LCC2 and MCF7 cell viability, with the effect being more significant on LCC2. Mechanistically, TAM/HCA co-treatment decreases the expression level of ACLY in LCC2 by 74 %, while in MCF7 by only 59 %. Moreover, apoptosis marker caspase-3 and Bax were increased, while the anti-apoptotic Bcl2 was decreased. Furthermore, the cholesterol and TG contents were increased in LCC2 than in MCF7. Our data revealed that ACLY plays a key role in TAM resistance and ACLY inhibition by HCA-mediated sensitization of BC-resistant cells to TAM.

ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer.

Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3' untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC.