Effect of High-intensity Laser Therapy on Carpal Tunnel Syndrome Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: To provide a strong foundation for the use of high-intensity laser therapy (HILT) in carpel tunnel syndrome (CTS,) we conducted a systematic review and meta-analysis to investigate the outcomes of short- and long-term follow-up studies. DESIGN: Systematic review and meta-analysis. RESULTS: Sample sizes of included studies ranged from 16 to 98 patients (total N = 308). Overall, a significant difference between the treatment and control groups were found across majority of the measures. Studies using a four-week follow-up period, however, only found significantly greater benefits for HILT in visual analogue scale (VAS) compared to placebo (p = 0.0191), Transcutaneous electrical nerve stimulation (TENS) (p = 0.0026), and low-intensity laser therapy-20 J/cm2 (p < 0.0002), and exercise (p < 0.0001). For improvement in VAS score over a long treatment period, HILT was also preferred over control group (p < 0.0071). Insufficient evidence exists to determine effect of HILT on nerve conduction examinations. The only statistically significant differences observed in examinations were in relation to sensory nerve action potential (p = 0.0083) and sensory nerve conduction velocity (SNCV) (p = 0.0468). CONCLUSION: Moderate evidence exists regarding efficacy of HILT compared to placebo, HILT + wrist splint, and exercise in a short period of follow-up time but evidence on long-term follow-up is limited.

From diagnosis to resistance: a symphony of miRNAs in pheochromocytoma progression and treatment response.

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.

Clinical significance of vit D and AMH and its correlation with polycystic ovarian parameters in obese and non-obese Egyptian women.

Women of reproductive age are frequently affected by the heterogeneous endocrine-metabolic conditions recognized as polycystic ovarian syndrome (PCOS). Moreover, FSH (Follicle-stimulating hormone), steroidogenesis, and LH (Luteinizing Hormone) are suppressed by the anti-Mullerian hormone, a good indicator of ovarian reserve, that is generated from granulosa cells. In the past ten years, vitamin D (VD) has attracted and maintained great interest in human health and biomedical research, particularly those about female reproductive-metabolic problems. Therefore, this study was designed to evaluate the correlation of VD and AMH with PCOS parameters in Egyptian women. Assessments were done on 35 control women and 45 PCOS sufferers. Utilizing the updated Rotterdam criteria, PCOS was identified. After recording anthropometric data, fasting serum levels of VD, follistatin (FST), insulin, FSH, LH, total testosterone (TT), sex hormone binding globulin (SHBG), as well as fasting plasma glucose (FPG), and the free androgen index (FAI) were measured in both groups. Compared to the control group, the PCOS group had a greater prevalence of hypovitaminosis D but serum levels of follistatin, LH, TT, AMH, insulin, and FPG, were considerably higher. Besides, there was a substantial inverse relationship between VD and the levels of follistatin, FPG, LH, TT, and AMH and a positive correlation with FSH in PCOS women's blood. This study revealed that hypovitaminosis D, elevated AMH, and FST may be regarded as alarming risk factors for PCOS in Egyptian women.

Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction.

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.

miRNAs driving diagnosis, progression, and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.

Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

New indole derivatives as multitarget anti-Alzheimer's agents: synthesis, biological evaluation and molecular dynamics.

Background: Alzheimer's disease is a neurological disorder that causes brain cells to shrink and die. Aim: Thirteen novel 'oxathiolanyl', 'pyrazolyl' and 'pyrimidinyl' indole derivatives were designed and synthesized as anti-Alzheimer's disease treatment. Method: In vitro enzyme assay was performed against both AChE and BChE enzymes. In addition, antioxidant assay and cytotoxicity on a normal cell line were determined. Molecular docking and dynamic simulations were conducted to confirm the binding mode in both esterases' active sites. In silico absorption, distribution, metabolism, excretion and toxicity studies were also carried out. Results & conclusion: Compounds 5, 7 and 11 exhibited superior inhibitory activity against acetylcholinesterase and butyrylcholinesterase, with IC50 values of 0.042 and 3.003 µM, 2.54 and 0.207 µM and 0.052 and 2.529 µM, respectively, compared with donepezil.

The role of miRNAs in laryngeal cancer pathogenesis and therapeutic resistance - A focus on signaling pathways interplay.

Laryngeal cancer (LC)is the malignancy of the larynx (voice box). The majority of LC are squamous cell carcinomas. Many risk factors were reported to be associated with LC as tobacco use, obesity, alcohol intake, human papillomavirus (HPV) infection, and asbestos exposure. Besides, epigenetics as non-coding nucleic acids also have a great role in LC. miRNAs are short nucleic acid molecules that can modulate multiple cellular processes by regulating the expression of their genes. Therefore, LC progression, apoptosis evasions, initiation, EMT, and angiogenesis are associated with dysregulated miRNA expressions. miRNAs also could have some vital signaling pathways such as mTOR/P-gp, Wnt/-catenin signaling, JAK/STAT, KRAS, and EGF. Besides, miRNAs also have a role in the modulation of LC response to different therapeutic modalities. In this review, we have provided a comprehensive and updated overview highlighting the microRNAs biogenesis, general biological functions, regulatory mechanisms, and signaling dysfunction in LC carcinogenesis, in addition to their clinical potential for LC diagnosis, prognosis, and chemotherapeutics response implications.

A spotlight on the interplay of signaling pathways and the role of miRNAs in osteosarcoma pathogenesis and therapeutic resistance.

Osteosarcoma (OS) is one of the most common bone cancers that constantly affects children, teenagers, and young adults. Numerous epigenetic elements, such as miRNAs, have been shown to influence OS features like progression, initiation, angiogenesis, and treatment resistance. The expression of numerous genes implicated in OS pathogenesis might be regulated by miRNAs. This effect is ascribed to miRNAs' roles in the invasion, angiogenesis, metastasis, proliferation, cell cycle, and apoptosis. Important OS-related mechanistic networks like the WNT/b-catenin signaling, PTEN/AKT/mTOR axis, and KRAS mutations are also affected by miRNAs. In addition to pathophysiology, miRNAs may influence how the OS reacts to therapies like radiotherapy and chemotherapy. With a focus on how miRNAs affect OS signaling pathways, this review seeks to show how miRNAs and OS are related.

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.

Significance of miRNAs on the thyroid cancer progression and resistance to treatment with special attention to the role of cross-talk between signaling pathways.

Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. It has many types, the Papillary thyroid cancer (PTC)(most common and follicular thyroid carcinoma (FTC). Several risk factors have been associated with TC radiation exposure, autoimmunity, and genetics. Microribonucleic acids (miRNAs) are the most important genetic determinants of TC. They are small chains of nucleic acids that are able to inhibit the expression of several target genes. They could target several genes involved in TC proliferation, angiogenesis, apoptosis, development, and even resistance to therapy. Besides, they could influence the stemness of TC. Moreover, they could regulate several signaling pathways such as WNT/ß-catenin, PI3K/AKT/mTOR axis, JAK/STAT, TGF- ß, EGFR, and P53. Besides signaling pathways, miRNAs are also involved in the resistance of TC to major treatments such as surgery, thyroid hormone-inhibiting therapy, radioactive iodine, and adjuvant radiation. The stability and sensitivity of several miRNAs might be exploited as an approach for the usage of miRNAs as diagnostic and/or prognostic tools in TC.

miRNAs role in bladder cancer pathogenesis and targeted therapy: Signaling pathways interplay - A review.

Bladder cancer (BC) is the 11th most popular cancer in females and 4th in males. A lot of efforts have been exerted to improve BC patients' care. Besides, new approaches have been developed to enhance the efficiency of BC diagnosis, prognosis, therapeutics, and monitoring. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. The miRNAs are either downregulated or upregulated in BC due to epigenetic alterations or biogenesis machinery abnormalities. In BC, dysregulation of miRNAs is associated with cell cycle arrest, apoptosis, proliferation, metastasis, treatment resistance, and other activities. A variety of miRNAs have been related to tumor kind, stage, or patient survival. Besides, although new approaches for using miRNAs in the diagnosis, prognosis, and treatment of BC have been developed, it still needs further investigations. In the next words, we illustrate the recent advances in the role of miRNAs in BC aspects. They include the role of miRNAs in BC pathogenesis and therapy. Besides, the clinical applications of miRNAs in BC diagnosis, prognosis, and treatment are also discussed.

Innovative Use of Biodex Balance System to Improve Dynamic Stabilization and Function of Upper Quarter in Recreational Weightlifters: A Randomized Controlled Trial.

Background and Objectives: Following an injury, upper-body strength and proprioception training is typically suggested. To our understanding, no prior research has looked into the impact of balance training on upper-body strength and stability. So, this study investigated the effects of Biodex balance training on enhancing the dynamic stability, strength, and function of the upper quarter (UQ) in recreational weightlifters. Materials and Methods: Fifty male weightlifters were randomly assigned into two groups. The experimental group received an upper-extremity Biodex balance training program three times/week for eight weeks, while the control group underwent a regular weightlifting training routine. Pre- and post-test scores of the upper-quarter dynamic stability, strength, and function were measured for both groups using the shoulder active repositioning accuracy test, two-minute push-up test, and the upper-quarter Y-balance test (UQ-YBT) and one-arm hop test, respectively. Results: Post-test values were significantly greater for the normalized UQ-YBT test than pre-test values in both groups (p < 0.05). Post-test values of the experimental group were significantly greater than the control group (p < 0.05). Regarding the shoulder active repositioning accuracy test and the time of the one-arm hop test, post-test values were significantly lower than pre-test values for both groups (p < 0.05), and post-test values of the experimental group were significantly lower than those of the control group (p < 0.05). The post-test value of the two-minute push-up test of each group was significantly higher than the pre-test value (p < 0.05), without any significant difference between both groups (p > 0.05). Conclusions: Adding upper-body Biodex balance training to a regular weightlifting training routine was effective in enhancing the upper quarter's dynamic stability and function.

Ambroxol, a mucolytic agent, boosts HO-1, suppresses NF-κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF-κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti-inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO-1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF-κB signaling and its consequent target pro-inflammatory mediators, IL-6 and TNF-α. In contrast, IL-10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti-inflammatory, antioxidant, and antiapoptotic properties.

Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity.

Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives (4-15) was designed and synthesised as novel CDK2 inhibitors. The anti-proliferative activities against MCF-7, HCT-116, and HepG-2 were used to evaluate their anticancer activity as novel CDK2 inhibitors. Most of the compounds showed superior cytotoxic activity against MCF-7 and HCT-116 compared to Sorafenib. Only compounds 8, 14, and 15 showed potent activity against HepG-2. The CDK2/cyclin A2 enzyme inhibitory activity was tested for all synthesised compounds. Compound 15 showed the most significant inhibitory activity with IC50 0.061 ± 0.003 µM. It exerted remarkable alteration in Pre G1 and S phase cell cycle progression and caused apoptosis in HCT cells. In addition, the normal cell line cytotoxicity for compound 15 was assigned revealing low cytotoxic results in normal cells rather than cancer cells. Molecular docking was achieved on the designed compounds and confirmed the two essential hydrogen binding with Leu83 in CDK2 active site. In silico ADMET studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity.

Pulmonary Function and Aerobic Capacity Responses to Equine Assisted Therapy in Adolescents with Idiopathic Scoliosis: A Randomized Controlled Trial.

BACKGROUND: Idiopathic scoliosis is a common spinal malalignment that negatively impacts the respiratory system and physical conditioning in adolescents. Equine-assisted therapy comprises therapeutic horseback riding that optimizes physical performance and mobility in a range of contexts. However, the influence of equine-assisted therapy on pulmonary function remains unclear. OBJECTIVE: To examine the impact of 10 weeks of hippotherapy combined with Schroth exercises on pulmonary function and aerobic capacity in adolescents with idiopathic scoliosis. METHODS: A randomized controlled trial including 45 patients, randomly assigned to experimental and control groups, was performed. Patients in the experimental group received 15 30-min sessions of hippotherapy over a period of 10 weeks. The 2 groups attended a 60-min session of Schroth exercises 3 times/week for 10 weeks. Pulmonary function and functional capacity were assessed before and after the intervention. RESULTS: Pre- and post-intervention variables (FVC, FEV1, FEV1/FVC, MVV and 6MWT) revealed significant improvement in both groups (p < 0.05). The improvement in the experimental group was significantly higher than in the control group (p < 0.05). CONCLUSION: The addition of hippotherapy to Schroth exercises resulted in improved pulmonary function and aerobic capacity in adolescents with idiopathic scoliosis.

First trimester fetal echocardiography limitations and its expected clinical values.

BACKGROUND: Fetal cardiac activity could be observed between 6th and 7th gestational weeks, early performance of fetal echocardiography could be implemented to screen for fetal heart disease. The effectiveness of early first trimester fetal echocardiography has not been adequately investigated, especially with modern sonographic technological advances. The purpose of the study is to evaluate the capability to visualize fetal cardiac structures within the first trimester as early as 10th gestational weeks and to elucidate the value of using color Doppler in visualization of cardiac structures within early gestation. A prospective clinical trial conducted on 150 study subjects, 44 of them were twin gestations. Cases were fully assessed by fetal echocardiographic examination from 10th gestational week to 13 gestational weeks in a sequential manner weekly. The research study was conducted at cardiology department fetal unit in one of the tertiary hospitals. RESULTS: Four chamber view was mostly visualized from 12 gestational weeks, whereas cardiac axis was fully visualized in all cases from 12 gestational weeks; on the other hand, IVC assessment by 2D was satisfactorily visualized in 78.26% of cases and by color Doppler in 82.61% of cases at 13 gestational weeks, pulmonary veins were visualized in 21.74% of cases by 2D and 43.5% of cases by color Doppler at 13 gestational weeks, and interestingly, ventricular inflows were satisfactorily visualized in almost all cases from 10th gestational weeks. CONCLUSIONS: First trimester fetal echo is an outstanding enhancement in management pathways of cases susceptible to have fetal cardiac abnormalities permitting early detection of structural cardiac anomalies triggering a cascade of scanning for extra cardiac anomalies to aid in evaluation and assessment of the best management course for those affected cases.

Impact of antenatal oxytocin infusion on neonatal respiratory morbidity associated with elective cesarean section.

INTRODUCTION: This study was designed to estimate respiratory morbidity associated with elective cesarean section (ECS) and to determine the effect of antenatal oxytocin exposure on this morbidity. MATERIAL AND METHODS: Nine hundred and sixty-five neonates ≥ 37 weeks' gestation delivered by cesarean section during 1 year were included in this retrospective study and classified into two groups according to oxytocin exposure before cesarean deliveries. Respiratory morbidity for each group was recorded and statistically analyzed. RESULTS: Transient tachypnea of newborn (TTN) was significantly more frequent in group II (ECS group) than in group I (cesarean section after oxytocin exposure) (8.19% vs. 2.92%; respectively, p = 0.0006). Mechanical ventilation, continuous positive airway pressure (CPAP) and oxygen therapy were significantly more frequent in group II than in group I (1.78%, 2.14% and 4.28% versus 0.44%, 0.58% and 1.46%, respectively; p = 0.039, and p = 0.033 and p = 0.009, respectively). The number of newborns admitted to the neonatal unit and neonatal intensive care unit (NICU) was significantly higher in group II than in group I (6.41% and 2.14% vs. 2.05% and 0.58%, respectively; p = 0.001 and p = 0.033, respectively). Surfactant, fluid therapies and parenteral nutrition were significantly more frequent in group II than in group I (2.14%, 4.28% and 2.49% vs. 0.15%, 1.46% and 0.73%, respectively; p = 0.001, p = 0.009 and p = 0.02, respectively). CONCLUSIONS: Neonatal respiratory morbidity associated with ECS significantly decreased after antenatal oxytocin exposure. A significant reduction of neonatal respiratory morbidity would be achieved if ECS were performed after 39 weeks' gestation.

Efficacy and safety of post-cesarean section incisional infiltration with lidocaine and epinephrine versus lidocaine alone in reducing postoperative pain: A randomized controlled double-blinded clinical trial.

OBJECTIVE: Aim was to assess the efficacy and safety of incisional infiltration of lidocaine and epinephrine vs. lidocaine only to reduce postcesarean section (C/S) pain. MATERIAL AND METHODS: It was a prospective, randomized, controlled, double-blinded clinical trial that was conducted in two tertiary hospitals in Egypt and included 153 women undergoing C/S under general anesthesia. They were randomly divided into the following two groups: Group I (control group, number=78), in which the wound was infiltrated before skin closure with 20 mL of 2% lidocaine, and Group II (study group, number=75), in which the wound was infiltrated before skin closure with 20 mL of 2% lidocaine and epinephrine. The primary outcomes were the time to first analgesic (TFA) request (minutes) and the postoperative pain scores that were measured using a visual analogue scale (VAS). The secondary outcomes included the duration of C/S, onset of mobilization, onset of breastfeeding, duration of hospital stay, local or systemic side effects of lidocaine and epinephrine, postoperative pyrexia, and postoperative wound infection. RESULTS: The pain score determined using VAS after 1 and 2 h was significantly decreased in Group II than in Group I. However, at 4.8 and 16 h, these results were significantly reversed in Group II than in Group I. The cumulative postoperative opioid consumption was significantly less in Group II than in Group I (50 vs. 90 mg). The onset of mobilization, onset of breastfeeding, and duration of hospital stay was significantly shorter in Group II than in Group I, whereas the TFA request was significantly longer in Group II. CONCLUSION: Administering epinephrine with 2% lidocaine prolongs the anesthetic effect and reduces the opioid analgesic dose postoperatively required, thereby enhancing patient recovery.