Radiation therapy outcomes of patients with pituitary macroadenoma.

Pituitary adenomas are one of the most common benign intracranial tumors, which are normally treated with surgery along with radiation therapy and medication such as dopamine agonist in prolactinoma. The aim of the present study was to evaluate the outcome of patients with pituitary macroadenoma who underwent radiation therapy. For the present retrospective study, a total of 75 patients with pituitary macroadenoma who received radiation therapy were included. Data was acquired from the electronic medical record system of the hospital. Mean ± standard deviation of the quantitative variables, such as age and sizes of the tumors, were reported. In addition, frequencies and percentages were presented for all categorical variables. To compare the frequency distribution in radiation therapy characteristics between functional and non-functional tumors, the χ2 test or Fisher's exact test was applied, where appropriate. Kaplan-Meier survival curve was drawn to assess the progression free survival proportion. P≤0.05 was considered to indicate a statistically significant difference. In the present study, all patients (n=75) with pituitary macroadenoma were treated with radiation therapy (RT). The mean age was 38.55±1.36 years and the majority of the patients were male (43; 57.3%). The mean tumor size was 3.84±1.43 cm. In total, 66.7% were non-functional tumors whereas 33.3% were functional tumors that produce hormones in excess [growth hormone (72%), prolactin (16%), both growth hormone and prolactin (8%) and adrenocorticotropic hormone (4%)]. The overall outcome was revealed to be 92% achieving local tumor control and 28% achieving biochemical control. Hypopituitarism (38.7%) and visual acuity deterioration (9.3%) were the most common complications observed following RT. The overall progression-free survival at 2 years was 92%. In conclusion, the data of the present study suggested that local tumor control in non-functional and functional pituitary macroadenoma can be well managed with RT. However, biochemical control to normalize hormones overproduction in functional pituitary macroadenoma was not as effective as local tumor control.

Clinical utility of ozone therapy and hyperbaric oxygen therapy in degenerative disc disease.

Ozone can be medically useful concerning healing wounds and relieving pain in various conditions, such as disc disease. The aspects of human blood ozonation have been reviewed, as well as potential complications that may arise. The mechanisms of ozone therapy are discussed in detail. It is imperative to recognize ozone as a useful proxy in oxidative-stress related diseases, consolidating other medical gases recognized for their therapeutic importance. The utility of hyperbaric oxygen therapy is also discussed. Disc herniation is very common, as more than 3 million cases are treated per year. Herein we review the medical, surgical, and gene-based therapies that ozone therapy can provide regarding disc disease.

Prolactinoma: Clinical Characteristics, Management and Outcome.

Aim Prolactinoma, a prolactin (PRL) secreting functioning pituitary tumor, is the most common of all pituitary adenomas (PA) accounting for 40-60% and dopamine agonists (DA) are the cornerstone of treatment. The aim of this study was to review the clinical presentation, treatment modalities and therapeutic outcomes of patients with prolactinomas in the South Asia region. Methods This retrospective study was conducted in the Endocrinology Department of Shaukat Khanum Memorial Cancer Hospital and Research Centre from December 2011 till December 2019. Medical records were used to retrieve for patient's demographics, clinical features at diagnosis, PRL levels and size of prolactinoma on MRI at diagnosis and after start of dopamine agonists and outcome of medical management. Results A total of 107 patients were included in this study. Mean age at diagnosis was 35 (22-54) years for men and 32 (18-50) years for women and 66.4% (71) of the patients were females. Our study included 38 (35.5%) microadenoma, 50 (46.7%) macroadenoma and 19 (17.8%) giant adenomas. At presentation, the most common symptom among females was menstrual irregularity/amenorrhea seen in 73.2% of females and among males was visual disturbance (80.6%). A significant reduction in PRL levels was seen within six to 12 months of treatment. Mean PRL levels decreased from 3162.8 ng/ml to 1.52 ng/ml. A notable decrease in tumor size was seen with medical management, mean adenoma size decreased from 2.18 cm to 1.04 cm. With cabergoline (CAB) 83.3% biochemical cure was seen compared to bromocriptine (BRC) which has 60.4%. The radiological response rate in CAB and BRC groups was 65.45% and 60%, respectively. Complete resolution of adenoma was seen in 13 patients (nine were microadenoma, two macro and two giant adenomas). The prolactin level at diagnosis was positively correlated with maximum tumor diameter (r = 0.469, P = 0.001). Two patients developed cerebrospinal fluid (CSF) rhinorrhea and the defect was repaired in both patients. Median follow-up duration was 40 (12-288) months. Conclusion Clinical presentation and demographics of prolactinoma are the same in our region when compared to the rest of the world. Cabergoline is superior to bromocriptine in prolactin normalization and tumor shrinkage but still bromocriptine is being used in a significant number of patients in low-income countries as first-line due to its low cost.

Surfer's myelopathy: A review of etiology, pathogenesis, evaluation, and management.

Context: Surfer's myelopathy (SM) is an acute syndrome identified by nontraumatic paraparesis or paraplegia. Though traditionally tied to first-time surfers, the condition encompasses any activity involving hyperextension of the back such as gymnastics, yoga, and Pilates.Methods: MEDLINE® and Google Scholar literature searches were gathered to identify relevant case reports for determining the etiology, pathogenesis, evaluation, and management of SM.Results: While the rare nature of SM limits its full understanding, studies have pinpointed that hyperextension in the back leads to vasculature insufficiency secondary to dynamic compression of the artery of Adamkiewicz. In surfing, this hyperextension combined with the execution of the Valsalva maneuver while trying to stand up on the surfboard likely increases intraspinal pressure. Due to its nontraumatic origin, the presence of SM is not immediately clear. Moreover, its similarity in clinical and radiological presentations with other entities can further complicate diagnosis. Seemingly, idiopathic urological symptoms can be explained by the physician if they conduct a thorough history.Conclusion: In an effort to raise awareness for the practicing physician, we presently review the etiology, diagnosis, treatment, and prolonged effects of SM. With the surging popularity of surfing as well as the advent of children participating in precarious sports and activities at an earlier age, we can expect a rising incidence of traumatic and nontraumatic spinal cord injuries. Neurologists, urologists, emergency medicine and sports medicine physicians alike can utilize this review to build a high index of suspicion for SM. The risk factors for SM should be conveyed to those participating in novices in surfing, yoga, gymnastics, ballet, and any activity enabling sustained or repeated spinal extension. Increased general awareness will facilitate increased symptom recognition in order to arrest aggravation of injury.

Cerebrospinal fluid leaks secondary to dural tears: a review of etiology, clinical evaluation, and management.

OBJECTIVE: Damage to the dura mater often occurs in trauma cases of the head and spine, surgical procedures, lumbar punctures, and meningeal diseases. The resulting damage from dural tears, or durotomy, causes cerebrospinal fluid (CSF) to leak out into the surrounding space. The CSF leak induces intracranial hypotension, which can clinically present with a range of symptoms not limited to positional headaches which can confound accurate diagnosis. Current methods of evaluation and management of dural tears are discussed herewith, as well as the present understanding of its etiology, which may be classified as related to surgery, procedure, trauma, or connective tissue disorder. METHODS: We piloted a MEDLINE® database search of literature, with emphasis on the previous five years, combining keywords such as "cerebrospinal fluid leak," "surgery," "procedure," and "trauma" to yield original research articles and case reports for building a clinical profile. RESULTS: Patients with suspected dural tears should be evaluated based on criteria set by the International Headache Society, radiological findings, and a differential diagnosis to accurately identify the tear and its potential secondary complications. Afflicted patients may be treated promptly with epidural blood patches, epidural infusions, epidural fibrin glue, or surgical repair. At this time, epidural blood patches are the first line of treatment. Dural tears can be prevented to an extent by utilizing minimally invasive techniques and certain positions for lumbar puncture. Surgical, trauma, lumbar puncture, and epidural injection patients should be observed very carefully for dural tears and CSF leaks as the presenting clinical manifestations can be highly individualized and misguiding. CONCLUSION: Because studies have demonstrated a high frequency of dural tears, particularly in spinal surgery patients, there is a need for prospective studies so that clinicians can develop an elaborate prevention strategy and response to avoid serious, unseen complications.

Myasthenia Gravis Mimicking Third Cranial Nerve Palsy: A Case Report.

Background: The most common pituitary adenoma presentation is a visual field defect and inappropriate pituitary hormone secretion. The compression of the optic chiasm causes visual impairment. Large pituitary adenomas can rarely cause diplopia and ptosis secondary to adenoma's lateral extension into the cavernous sinus. Myasthenia gravis is an autoimmune disorder involving neuromuscular junctions. It is characterised by skeletal muscle fatigability, commonly involving extraocular muscles, face and limbs. It is estimated that 75% of myasthenia gravis patients present with ptosis and diplopia. The association of myasthenia gravis with pituitary adenoma is very rare. Case Description: A 30-year-old lady presented with headache, diplopia and ptosis of the left eye for 2 months. She was diagnosed with acromegaly secondary to pituitary adenoma. Ptosis is a rare presenting feature in pituitary adenoma. Her case was discussed in a multidisciplinary meeting, and the consensus was that her ptosis is likely secondary to pituitary adenoma, which was involving the left cavernous sinus. She underwent transsphenoidal resection of pituitary macroadenoma. Three weeks post-surgery, she developed bilateral ptosis, dysarthria and dysphonia, which was diagnosed as myasthenia gravis. Clinical Implications: Ptosis is a rare manifestation of pituitary adenoma. Nonetheless, pituitary tumour patients presenting with ptosis should be evaluated for the neuromuscular disorder. A high index of suspicion is required for early diagnosis and prompt treatment of myasthenia gravis.

The Role of Diabetes Mellitus in Diseases of the Gallbladder and Biliary Tract.

BACKGROUND: The increasing prevalence of diabetes mellitus worldwide continues to pose a heavy burden. Though its gastrointestinal impact is appropriately recognized, the lesser known associations may be overlooked. OBJECTIVE: We aim to review the negative implications of diabetes on the gallbladder and the biliary tract. METHODS: A MEDLINE® database search of literature was conducted with emphasis on the previous five years, combining keywords such as "diabetes," "gallbladder," and "biliary". RESULTS: The association of diabetes to the formation of gallstones, gallbladder cancer, and cancer of the biliary tract are discussed along with diagnosis and treatment. CONCLUSION: Though we uncover the role of diabetic neuropathy in gallbladder and biliary complications, the specific individual diabetic risk factors behind these developments is unclear. Also, in addition to diabetes control and surgical gallbladder management, the treatment approach also requires further focus.

Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment.

BACKGROUND: Advances in treatment and increased awareness have improved the prognosis for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of 3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and secondary comorbidities. Previous research has provided evidence that increased renal sympathetic nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation (RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However, recent clinical trials have called into question RDN's efficacy. Numerous limitations must be addressed to discern the true effectiveness of RDN as a therapeutic option for RH. OBJECTIVE: We aimed to review the current understanding of RH, the anatomy of renal arteries, physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN as a treatment option, and all relevant clinical trials treating RH with RDN. METHODS: We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with emphasis on the previous five years, combining keywords such as "resistant hypertension" and "renal denervation." CONCLUSION: A plethora of information is available regarding heightened RSNA leading to RH. RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical understanding per individual basis, stricter guidelines regarding study design, increased operator experience, and integrating the use of a multielectrode catheter.

Revisiting the pineal gland: a review of calcification, masses, precocious puberty, and melatonin functions.

Introduction: The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement and curiosity. Methods: We review present an up-to-date review including the anatomy, embryology, and physiology of the pineal gland and its ability to secrete hormones including melatonin, pathophysiology of pineal gland tumors, cysts, and calcifications, their clinical presentation including their association with parkinsonism and precocious puberty, and various treatment approaches. Results: Exploring the biochemistry of melatonin, various calcification morphologies, and pineal tumors may uncover a wider role and the exhaustive case study consolidation allows clinicians to carefully review the literature and aid their treatment approaches. Conclusion: It is imperative that clinicians and diagnosticians are able to distinguish manifestations of an overlooked gland.

Juxtaglomerular Cell Tumor: Reviewing a Cryptic Cause of Surgically Correctable Hypertension.

Juxtaglomerular cell tumor (JGCT), or reninoma, is a typically benign neoplasm generally affecting adolescents and young adults due to modified smooth muscle cells from the afferent arteriole of the juxtaglomerular apparatus. Patients experience symptoms related to hypertension and hypoka-lemia due to renin-secretion by the tumor. MRI, PET, CT, and renal vein catheterizations can be used to capture JGCTs, with laparoscopic ultrasonography being most cost-efective. Surgical removal is the best option for management; electrolyte imbalances are a potential complication which may be assuaged via pre-surgical administration of aliskiren, a renin inhibitor. Considering the vast etiology for hypertension and rarity of JGCT, the diagnosing physician must have a high index of suspicion for JGCT. Early recognition and management can help prevent cardiovascular or pregnancy complications and fatalities, vascular invasion and metastasis, improve quality of life, and limit socioeconomic liabilities. Herein we review the epidemiology, genetics, histopathol-ogy, clinical presentation, and management of this rare condition. The impact of genetics on prognosis warrant further research.

Clinical utility of ozone therapy in dental and oral medicine.

Ozone is a highly reactive compound composed of three oxygen atoms that acts as an oxidant and oxidizer. It exists at the ground level as an air pollutant and a constituent of urban smog, as well as in the Earth's upper atmosphere as a protective layer from ultraviolet rays. Healthy cells contain antioxidants such as vitamins C and E to protect against ozone oxidization. However, pathogens such as bacteria contain very trace amounts of antioxidants in their membranes, which make them susceptible to ozone and destroy the cell membrane. This review explores the history, composition, and use of ozone worldwide in dentistry. Ozone therapy has thus far been utilized with wound healing, dental caries, oral lichen planus, gingivitis and periodontitis, halitosis, osteonecrosis of the jaw, post-surgical pain, plaque and biofilms, root canals, dentin hypersensitivity, temporomandibular joint disorders, and teeth whitening. The utility of ozone will undoubtedly grow if studies continue to show positive outcomes in an increasing number of dental conditions.

Current understanding of tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncologic emergency from the intracellular release of material in lysing malignant cells. The earlier it is treated, the less likely it is to be harmful to an individual and spread through the body. Common complications of TLS include arrhythmias, which are caused by hypocalcemia or hyperkalemia, renal failures due to hyperuricemia or hyperphosphatemia, and seizures. Furthermore, the risk to develop TLS varies widely based on several factors including factors that are related to disease, the patient, and the treatment of the patient. Laboratory data can be used to gauge the severity of TLS based on patient serum levels for specific markers. On the contrary, evidence of TLS via radiological imaging and electrocardiogram findings has been a limited way to evaluate TLS, indicating the need for further research in this area. Common trends of treatment have also been seen in the past several years, evident by case studies seen in the following literature review.

Etiology, Diagnosis, and Management of Seminal Vesicle Stones.

BACKGROUND/AIMS: Seminal vesicle (SV) stones are a rare, and thus readily misdiagnosed condition in practice. Understanding the etiology, diagnosis, and management are crucial to guide a urologist's care, and are provided in this literature review. METHODS: The inclusion criteria for the literature search, using the search engines MEDLINE® and PubMed was conducted using a combined query of "seminal vesicle stone" and the following keywords: calculi, hematospermia, calcification, and transrectal ultrasound (TRUS). RESULTS: The etiology of SV stones is currently unknown where majority of the patients present with having painful ejaculation and hematospermia. However, clinicians have reported potential etiologies by categorization as an inflammatory or non-in-flammatory. A majority of the previous cases had shown multiple stones being present in the SV duct system that are typically diagnosed through radiological examination such as TRUS, MRI, or plain radiographs. Amongst the many imaging approaches, TRUS remains the primary imaging diagnoses of SV calculi. Transurethral seminal vesiculoscopy has shown to be used in an abundant of the case reports to be an ideal surgical approach for managing small SV stones. In regard to larger stones, a transperitoneal laparoscopic protocol is proper. CONCLUSION: The current imaging techniques have increased the case reports and diagnosis of SV calculi; however, more research is warranted for understanding the pathogenesis of the formation of SV stones. An optimal management of the extraction of SV stones depends on a number of factors such as size and location.

Clinical utility of hyperbaric oxygen therapy in dentistry.

This fuller impact of the use of hyperbaric oxygen therapy within dentistry is taking greater notice with newer research findings. There are new advancements in research regarding postradiotherapy cases, osteonecrosis of the jaw, osteomyelitis, periodontal disease, and dental implants. Hyperbaric oxygen therapy can even be used in conjunction with other procedures such as bone grafting. Although the research and clinical utility has come a long way, there are several complications to be mindful of during the application of hyperbaric oxygen therapy.

Transcriptome analysis reveals regulatory framework for salt and osmotic tolerance in a succulent xerophyte.

BACKGROUND: Zygophyllum xanthoxylum is a succulent xerophyte with remarkable tolerance to diverse abiotic stresses. Previous studies have revealed important physiological mechanisms and identified functional genes associated with stress tolerance. However, knowledge of the regulatory genes conferring stress tolerance in this species is poorly understood. RESULTS: Here, we present a comprehensive analysis of regulatory genes based on the transcriptome of Z. xanthoxylum roots exposed to osmotic stress and salt treatments. Significant changes were observed in transcripts related to known and obscure stress-related hormone signaling pathways, in particular abscisic acid and auxin. Significant changes were also found among key classes of early response regulatory genes encoding protein kinases, transcription factors, and ubiquitin-mediated proteolysis machinery. Network analysis shows a highly integrated matrix formed by these conserved and novel gene products associated with osmotic stress and salt in Z. xanthoxylum. Among them, two previously uncharacterized NAC (NAM/ATAF/CUC) transcription factor genes, ZxNAC083 (Unigene16368_All) and ZxNAC035 (CL6534.Contig1_All), conferred tolerance to salt and drought stress when constitutively overexpressed in Arabidopsis plants. CONCLUSIONS: This study provides a unique framework for understanding osmotic stress and salt adaptation in Z. xanthoxylum including novel gene targets for engineering stress tolerance in susceptible crop species.

Protein misfolding and aggregation in neurodegenerative diseases: a review of pathogeneses, novel detection strategies, and potential therapeutics.

Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy. As such, the folding process can go awry in several different ways. The pathogenic basis behind most neurodegenerative diseases is that the disruption of protein homeostasis (i.e. proteostasis) at any level will eventually lead to protein misfolding. Misfolded proteins often aggregate and accumulate to trigger neurotoxicity through cellular stress pathways and consequently cause neurodegenerative diseases. The manifestation of a disease is usually dependent on the specific brain region that the neurotoxicity affects. Neurodegenerative diseases are age-associated, and their incidence is expected to rise as humans continue to live longer and pursue a greater life expectancy. We presently review the sequelae of protein misfolding and aggregation, as well as the role of these phenomena in several neurodegenerative diseases including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, transmissible spongiform encephalopathies, and spinocerebellar ataxia. Strategies for treatment and therapy are also conferred with respect to impairing, inhibiting, or reversing protein misfolding.

The anticancer potential of metformin on prostate cancer.

BACKGROUND: Prostate cancer (PCa) is characterized as the most frequent type of cancer in males. Recent research has suggested patients who have diabetes mellitus taking metformin (MF) have a lower risk of PCa. MF has antineoplastic effects such as adenosine monophosphate-activated protein kinase (AMPK)-dependent and independent mechanisms, suppression of androgen signaling pathway, and alterations of insulin-like growth factor-1 (IGF-1) signaling pathways that cause the growth and proliferation of PCa. Based on epidemiological factors, patients with diabetes mellitus may have a protective effect on PCa. METHODS: A literature search on MEDLINE® was conducted using a combined query of "prostate cancer" and "metformin" to yield publications unveiling the mechanisms of action, biological effects, epidemiological evidence, and research advances of MF with respect to PCa. RESULTS: Evidence has shown that MF has multiple antineoplastic effects through AMPK-dependent and independent mechanisms, the alteration of IGF-1 signaling pathways, suppression of the androgen receptor pathway, inhibition of the mTOR pathway, and lipogenesis. Conduction of meta-analysis suggests mortality benefit to patients who exhibit PCa when taking MF. Clinical trials have shown evidence, demonstrating MF to improving significantly. CONCLUSIONS: Herewith we review the literature regarding the numerous mechanisms of action of MF on PCa in order to decrease or repress the growth, proliferation, and differentiation of PCa cells. We analyze the molecular impacts of MF as well as adjunct therapies such as androgen deprivation therapy, aspirin, statin, or chemotherapy, proposing that MF may have a future role in the treatment protocol of PCa whether as a monotherapy or in combination with other drugs.

The Evolving Role of Shear Wave Elastography in the Diagnosis and Treatment of Prostate Cancer.

To forego misdiagnosis and biopsy-related complications, we explore a novel technique that embraces tissue elasticity to circumvent the current limitations in the accurate, non-invasive detection of prostate cancer. A MEDLINE® database search of literature pertinent to prostate elastography published in the last five years was guided using the following terms: tissue elasticity, ultrasound elastography, strain elastography, magnetic resonance elastography, and shear wave elastography. Ultrasound shear wave elastography (SWE) utilizes the propagation of induced shear waves to provide a quantitative measurement of elasticity of soft tissue. Studies attempting to prove SWE as a strong predictor of malignant prostatic tissue have validated its high specificity and sensitivity compared to the sub-50% range observed with magnetic resonance imaging or transrectal ultrasound. Because its median positive predictive value is also much higher than the sub-40% range attributed to more conventional techniques, SWE yields reduced false-negative biopsy rates. It furthermore exhibits higher intraobserver reproducibility compared to conventional ultrasound. Recent treatments have also utilized SWE for noninvasive prostate cancer tissue ablation. Future improvements include standardized cutoff ranges for quantifying elasticity of malignant tissue. The implementation of a scoring system to predict cancer aggressiveness and prognosis may eliminate the need for unwarranted repeat biopsies postdiagnosis.

Ozone therapy for diabetic foot.

Diabetic foot ulcers (DFU) are a burden to the diabetic community. With increasing medical bills, to unsuccessful treatment, those suffering from DFUs can use alternative therapeutics. First seen in the mid-1800s, ozone (O3) is thought to be unstable, due to inherent molecular nature. With the help of pharmaceutical science, various O3 treatments have flourished in the medical community to help those suffering from DFUs. Promising results are seen through numerous studies. Usually, a mixture of both O2 and O3 is seen in pressurized machines as administered to the foot ulcer. Foot ulcers, specifically DFUs, need to be assessed, cleaned, and treated as fast as possible for the fastest results. Results such as amputation can be seen if the foot is not attended to as soon as possible. With fast growing clinical trials in O3 therapy and quick administration of the O3, O3 therapy may be on the rise to be at the forefront of treating DFUs. Compelling evidence is seen in clinical trials, but more must be done to fully understand the role of O3 in DFUs.

Clinical utility of ozone therapy for musculoskeletal disorders.

Oxygen-ozone (O3) therapy serves as an alternative medical technique that increases the oxygen in the body along with the introduction of O3. O3 therapy has finally reached a level where the biological mechanisms of action have been understood, showing that they are in the domain of physiology, biochemistry, and pharmacology. Few clinical applications have been reviewed here as well as exemplifying that O3 therapy is particularly useful in musculoskeletal disorders. In the therapeutic range, O3 can be used as a more effective and safe substitute of standard medications. O3 therapy has been used for many years for its ability to inactivate various viruses, cancer, and acquired immune deficiency syndrome but is now making strides in the treatment of musculoskeletal disorders such as rheumatoid arthritis, lumbar facet joint syndrome, subacromial bursitis, carpal tunnel syndrome, osteoarthritis, hip bursitis, shoulder adhesive capsulitis, herniated disc, and temporomandibular joint disorder.