Primary Therapeutic Intervention Research Articles

Reversing the Effects of Tongue Thrusting Using Tongue Tamers

This case report presents the successful correction of a tongue thrusting habit in a 8-year-old patient using tongue tamers as the primary therapeutic intervention. The patient exhibited anterior open bite and misaligned dentition, both attributed to chronic tongue thrusting during swallowing and speech. A thorough clinical examination and orthodontic assessment confirmed the need for habit correction to prevent further malocclusion and aid in proper dental development. The treatment plan involved the placement of tongue tamers on the lingual surfaces of the maxillary anterior teeth, aimed at retraining the tongue to adopt a correct posture during swallowing. The patient was also provided with oral habit awareness exercises to reinforce the therapy. Follow-up evaluations at 3, 6, and 12 months revealed a significant reduction in tongue thrusting behavior, with a corresponding improvement in the patient’s dental alignment and closure of the anterior open bite. The successful outcome highlights the effectiveness of tongue tamers in correcting tongue thrusting when used in combination with patient cooperation and regular monitoring. This case supports the use of this minimally invasive intervention for habit correction in growing children, improving both functional and aesthetic dental outcomes.

Botulinum toxin treatment for hemifacial spasm: harmonising neurological and aesthetic outcomes.

Hemifacial spasm (HFS) represents a challenging cranial movement disorder primarily affecting the facial nerve innervated muscles, with significant prevalence among Asians. Botulinum toxin type A (BoNT/A) injections, established as a primary therapeutic intervention since FDA approval, offer considerable effectiveness in alleviating spasms, albeit accompanied by challenges such as temporary effects and potential adverse events including facial asymmetry. This comprehensive review underscores the crucial need for harmonising neurological benefits and aesthetic outcomes in HFS management. The discussion delves into the interplay between facial aesthetics and neurological objectives in BoNT/A injections, emphasising precise techniques, dosages, and site considerations. Distinct aspects in neurological and aesthetic domains are also examined, including detailing the targeted muscles and injection methodologies for optimal therapeutic and aesthetic results. Importantly, evidence regarding various BoNT/A formulations, recommendations, and reconstitution guidelines in both neurology and aesthetics contexts are provided, along with a schematic approach outlining the stepwise process for BoNT/A injection in HFS treatment, addressing critical areas such as orbicularis oculi muscle sites, eyebrow correction strategies, mid- and lower-face considerations, contralateral injection sites, and post-injection follow-up and complication management. By highlighting the culmination of neurological efficacy and facial esthetics in BoNT/A treatment for HFS patients, this review proposes a holistic paradigm to achieve balanced symptomatic relief and natural aesthetic expression, ultimately enhancing quality of life for individuals grappling with HFS.

Design of Three-Dimensional-Printed Compression Ring for Enhanced Wound Healing of Colorectal Anastomosis to Minimize Dehiscence and Leakage Post Colectomy

Abstract Bowel resection surgery, also known as colectomy, is a primary therapeutic intervention where a neoplastic or cancerous segment of the bowel is removed and an anastomosis constructed to reestablish intestinal continuity. Several techniques can be used to create the anastomosis, including mechanical staplers or manual sutures. A potentially life-threatening complication in colon anastomosis is dehiscence and leakage. Various contributing factors can hinder the formation of anastomosis, including technical failure (human error, staple malfunction), inflammation caused by foreign body response (sutures and staples), collagenolytic bacteria, and patient comorbidities (chemotherapy, old age, and obesity). Here, we report a three-dimensional (3D)-printed compression ring with electrical stimulation (ES) functionality to improve wound healing and anastomotic closure. The device consists of a one-way locking mechanism for initial deployment, an elastic band tightening mechanism to secure seal as tissue heals, and electrodes for electrical stimulation to enhance wound healing. The compression ring was assembled with 83.4±3.9 N of force and delivers 147.5±8.8 kPa of pressure to tissue, effectively restricting blood flow to the clamped tissue. This helps to create the anastomosis between remaining tissue on either side. Our design facilitates manual assembly without necessitating an additional delivery device. Electrical impedance analysis confirmed adequate tissue–electrode contact. We tested this device with ex vivo ovine intestinal tissue and confirmed that the compression ring was able to withstand up to 2.0±0.4 kPa intraluminal pressure immediately following installation. By combining mechanical strength and electrical stimulation, this device could potentially improve wound healing, anastomotic closure, and minimize the risk of leaks.

Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.

Characterization of the malignant cells and microenvironment of infantile fibrosarcoma via single-cell RNA sequencing.

Infantile fibrosarcoma (IFS) is the most prevalent soft tissue sarcoma in children under 1 year old and is known for its rapid growth. The tumor lacks specific immunohistochemical tumor marker and a general view of tumor microenvironment (TME). Its primary therapeutic intervention places patients at a risk of disability or mutilation. This study aimed to elucidate the universal transcriptional characteristics of IFS and explore novel targets for diagnosis and therapy using single-cell RNA sequencing (scRNA-seq). Fresh tissue samples of IFS for scRNA-seq were collected from four patients before other treatments were administered. We conducted cell clustering, inferring copy number variation from scRNA-seq (InferCNV) analysis, gene differential expression analysis, cell function evaluation, Pearson correlation analysis, and cell-cell and ligand-receptor interaction analysis to investigate the distinct ecosystem of IFS. According to the single-cell resolution data, we depicted the cell atlas of IFS, which comprised 14 cell populations. Through comparison with normal cells, the malignant cells were distinguished, and potential novel markers (POSTN, IGFBP2 and CTHRC1) were identified. We also found four various functional malignant cell subtypes, three of which exhibited cancer stem cells (CSCs) phenotypes, and investigated the interplay between these subtypes and nonmalignant cells in the TME of IFS. Endothelial cells and macrophages were found to dominate the cell-cell communication landscape within the microenvironment, promoting tumorigenesis via multiple receptor-ligand interactions. This study provides a comprehensive characterization of the tumor transcriptome and TME of IFS at the cellular level, offering valuable insights for clinically significant advancements in the immunohistochemical diagnosis and treatment of IFS.

Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress

PurposeDiabetic neuropathy (DN) is a notable complication of diabetes mellitus. The potential involvement of miR-146a in DN regulation is presently under investigation. Metformin, a commonly prescribed medication for diabetes, is the primary therapeutic intervention. This study aimed to unveil the potential protective effects of metformin on diabetic neuropathy and explore the mechanisms underlying its action. MethodSix-weeks male Sprague Dawley rats (n = 40) were randomly divided into 5 groups. The rat model of diabetic neuropathy (DN) was established by administering streptozotocin (STZ). To investigate the effects on the sciatic nerve and resident Schwann cells (RSCs), metformin and miR-146a mimics were administered, and our research explored the potential underlying mechanism. ResultThe sciatic nerve samples obtained from diabetic rats exhibited noticeable morphological damage, accompanied by decreased miR-146a expression (2.61 ± 0.11 vs 5.0 ± 0.3, p < 0.01) and increased inflammation levels (p65: 1.89 ± 0.04 vs 0.82 ± 0.05, p < 0.01; TNF-α: 0.93 ± 0.03 vs 0.33 ± 0.03, p < 0.01). Notably, the administration of metformin effectively ameliorated the structural alterations in the sciatic nerve by suppressing the inflammatory pathway (p65: 1.15 ± 0.05 vs 1.89 ± 0.04, p < 0.01; TNF-α: 0.67 ± 0.04 vs 0.93 ± 0.03, p < 0.01) and reducing oxidative stress (NO: 0.062 ± 0.004 vs 0.154 ± 0.004umol/mg, p < 0.01; SOD: 3.08 ± 0.09 vs 2.46 ± 0.09 U/mg, p < 0.01). The miR-146a mimics intervention group exhibited comparable findings. ConclusionThis study's findings implied that metformin can potentially mitigate diabetic neuropathy in rats through the modulation of miR-146a expression.

Obesity: the perfect storm for heart failure.

Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction. Multi-imaging modalities are required for appropriate recognition of subclinical systolic dysfunction typically associated with obesity, with echocardiography being the most cost-effective technique. Therapeutic approach in patients with obesity and HF is challenging, particularly regarding patients with preserved EF in which few strategies with high level of evidence are available. Weight loss is of extreme importance in patients with obesity and HF, being a primary therapeutic intervention. Sodium-glucose co-transporter-2 inhibitors have been recently introduced as a novel tool in the management of HF patients. The present review aims at analysing the most recent studies supporting pathogenesis, diagnosis, and management in patients with obesity and HF.

Nanosphere-reinforced polysaccharide self-healing hydrogels for infected wound healing

Bacterial infection remarkably impedes wound healing, with antibiotics traditionally serving as the primary therapeutic intervention. However, the escalating misuse of antibiotics and the emergence of bacterial resistance present substantial treatment challenges for infected wounds. Consequently, the development of antibiotic-free antimicrobial dressings holds pertinent research and clinical relevance. To this end, this study aimed to introduce an all-natural hydrogel dressing, amalgamating polyphenols and polysaccharides, exhibiting pronounced antibacterial and antioxidant properties without relying on antibiotics. First, we constructed curcumin-tannic acid‑zinc ion nanospheres (CTZN) through self-assembly. Our experimental results showed that the nanospheres had excellent biocompatibility, antioxidant, and antimicrobial abilities. Subsequently, we prepared carboxymethylated chitosan/oxidized sodium alginate hydrogels via Schiff base reactions. Incorporation of CTZN into the hydrogel system not only improves the inherent qualities of the hydrogel but also confers multifunctional properties, including antimicrobial, antioxidant, and anti-inflammatory abilities. In this study, we enhanced the physicochemical properties and biological activity of hydrogels by introducing natural material nanospheres, offering a novel approach that could pave the way for the development of purely natural biomaterial dressings.

Prognostic value of ultrasound in early arterial complications post liver transplant.

Liver transplantation is the primary therapeutic intervention for end-stage liver disease. However, vascular complications, particularly those involving the hepatic artery, pose significant risks to patients. The clinical manifestations associated with early arterial complications following liver transplantation are often nonspecific. Without timely intervention, these complications can result in graft failure or patient mortality. Therefore, early diagnosis and the formulation of an optimal treatment plan are imperative. Ultrasound examination remains the predominant imaging modality for detecting complications post liver transplantation. This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these conditions. Overall, ultrasound offers the advantages of convenience, safety, effectiveness, and non-invasiveness. It enables real-time, dynamic, and precise evaluation, making it the preferred diagnostic method for post-liver transplantation assessments.

Disseminated Thymic Carcinoma: Case Report and Discussion on Problems of Treatment

Thymic carcinoma (TC) is a rare epithelial malignancy often distinguished by significant local invasion and propensity for distant metastases. Representing approximately 20% of all thymic neoplasms, the primary therapeutic intervention for resectable tumors remains surgical resection. For those that are unresectable or metastatic, palliative platinum-based chemotherapy is standard. Despite these interventions, approximately 30% of these malignancies are already advanced upon initial presentation. The current 5-year survival rate for metastatic TC stands at approximately 38%, with a definitive optimal treatment regimen yet to be established. This case report delineates a comprehensive five-year clinical trajectory of a patient with advanced TC who exhibited resistance to systemic treatments but showed favorable response to stereotactic body radiation therapy (SBRT). Through this case, we underscore the potential of SBRT as a viable therapeutic alternative for select metastatic TC patients. In our case, SBRT exhibited reliable local tumor control in each treated site with minimal side effects. To better understand the possibility of treatment options for disseminated TC more cases should be collected.

An Efficient and Scalable Method for the Production of Immunogenic SARS-CoV-2 Virus-like Particles (VLP) from a Mammalian Suspension Cell Line.

The rapid evolution of new SARS-CoV-2 variants poses a continuing threat to human health. Vaccination has become the primary therapeutic intervention. The goal of the current work was the construction of immunogenic virus-like particles (VLPs). Here, we describe a human cell line for cost-efficient and scalable production of immunogenic SARS-CoV-2 VLPs. The modular design of the VLP-production platform facilitates rapid adaptation to new variants. Methods: The N, M-, and E-protein genes were integrated into the genome of Expi293 cells (ExpiVLP_MEN). Subsequently, this cell line was further modified for the constitutive expression of the SARS-CoV-2 spike protein. The resulting cell line (ExpiVLP_SMEN) released SARS-CoV-2 VLP upon exposure to doxycycline. ExpiVLP_SMEN cells were readily adapted for VLP production in a 5 L bioreactor. Purified VLPs were quantified by Western blot, ELISA, and nanoparticle tracking analysis and visualized by electron microscopy. Immunogenicity was tested in mice. Results: The generated VLPs contained all four structural proteins, are within the size range of authentic SARS-CoV-2 virus particles, and reacted strongly and specifically with immunoserum from naturally infected individuals. The VLPs were stable in suspension at 4 °C for at least 10 weeks. Mice immunized with VLPs developed neutralizing antibodies against lentiviruses pseudotyped with the SARS-CoV-2 spike protein. The flexibility of the VLP-production platform was demonstrated by the rapid switch of the spike protein to a new variant of concern (BA.1/Omicron). The present study describes an efficient, scalable, and adaptable production method of immunogenic SARS-CoV-2 VLPs with therapeutic potential.

Obstructive sleep apnea phenotypes eligible for pharmacological treatment

Obstructive sleep apnea (OSA) is a common disorder. Its prevalence is increasing worldwide, partially due to increasing rates of obesity, and OSA has a well-documented impact on physical health (increased risk of cardiovascular and metabolic disorders) and mental health, as well as major socioeconomic implications. Although continuous positive airway pressure treatment (CPAP) remains the primary therapeutic intervention for moderate to severe OSA, other treatment strategies such as weight loss, positional therapy, mandibular advancement devices (MAD), surgical treatment, myofunctional therapy of upper airways (UA) muscles and hypoglossal nerve stimulation are increasingly used. Recently, several trials have demonstrated the clinical potential for various pharmacological treatments that aim to improve UA muscle dysfunction, loop gain, or excessive daytime sleepiness. In line with the highly heterogeneous clinical picture of OSA, recent identification of different clinical phenotypes has been documented. Comorbidities, incident cardiovascular risk, and response to CPAP may vary significantly among phenotypes. With this in mind, the purpose of this review is to summarize the data on OSA phenotypes that may respond to pharmacological approaches.

Case report on Management and Outcomes of little Finger Amputation with Right Temporal–Parietal Region Injury with Schizophrenia.

Introduction : Little finger extremity traumatic amputation is a potentially life-changing event that frequently has significant physical, psychological, and occupational repercussions. particularly A deadly schizoaffective disorder outcome can be major self-mutilation, which is defined as self-inflicted bodily harm without suicidal intent. Self-amputation is one of two consequences seen in schizoaffective patients. Present complaints and Investigation : A 47-year-old female came to the accident and emergency department complaining of traumatic amputation of The distal portion of the little finger and the right temporal-parietal region were injured, which led to the complaints of nausea, vomiting, headache, weakness, and schizophrenia (15 years on medication). Past History : Since 16 years ago the patient had a history of schizophrenia. For additional care, they were hospitalized at Amravati Hospital. After being diagnosed with schizophrenia, she got positive outcomes following several specific tests and examinations. The primary diagnosis, therapeutic intervention, and outcomes : After a physical examination and investigation Based on the patient history and after diagnostic assessment observed that Acute subarachnoid hemorrhage is seen along the sulci of bilateral fronto-temporo-parietal lobes with the extension of hemorrhage along falx and tentorium tiny microhemorrhages contusion is seen in right basal gangly. Conclusions : Treatment is typically ongoing and frequently entails a triage of specialty care services, including medication, psychotherapy, and counselling.

Polytrauma with Grade-IV Liver Laceration and Grade-II Renal Laceration: A Case Report

Background: One of the leading causes of mortality and morbidity is road accidents. The commonest cause of polytrauma is due to road traffic accidents, other causes may include self-harming activities, suicide, and murder. Nearly two- thirds deaths due to Road Traffic accidents are reported in India mostly in the age group of 15-44 years. Rescue of patients with polytrauma requires maintaining hemostasis while concurrently administering treatments and using proper triage management according to the severity of the injuries, especially in situations of severe trauma with pulmonary contusion and significant blood loss. Massive hemothorax and extensive tracheobronchial hemorrhage result from serious lung injury. Depending on the amount of chest leakage in cases with hemothorax, emergency surgery is advised. Here we report a case of a 20-year-old adult male who was brought by his parents to the emergency department in a conscious state. The patient reported sustained injuries over the face, chest, and left knee. All the necessary laboratory investigations were done after which the patient was shifted to the Surgery Intensive Care Unit. The primary therapeutic intervention was given to the patient and was treated with blood transfusion, antibiotics, antiemetics, and antacids, and a diet was planned during hospitalization.

Case report on Management and Complication of Peutz Jegher Syndrome

Introduction: Infrequent and characterized by mucocutaneous pigmentations, gastrointestinal polyposis, and an increased risk of malignancy, Peutz-Jeghers syndrome is an autosomal dominant genetic condition. The usual perioral macules and patches that are colored in the buccal mucosa are present in 90% of patients, and numerous but not continuously contiguous lesions, primarily in the gastrointestinal (G.I.) tract, with rarely more than 20 hamartomata's polyps, are the characteristics of Peutz-Jeghers syndrome (P.J.S.). Present complaints and Investigation:-Suddenly felt sick to my stomach and started to puke. Abdominal pain, Black stools, repeated vomiting, weight loss of 5 kg in 15 days, loss of appetite, and Intussusception were discovered during examinations in the upper small bowel. A thorough study of the gastrointestinal tract was conducted. Endoscopically, the enormous polyps of the stomach and duodenum were discovered and biopsied. Resulting of bleeding due to the G.I. polyps, she became anemic. There were polyps. Later removed endoscopically while being sedated, C.T.'s Abdomen and pelvis found multiple mildly enhanced polypoidal lesions notes attached to the pyloric part of stomach and duodenum proximal jejunal loops, similar lesions of Ascending colon, transverse colon, and advice colonoscopy. History: The patient was admitted in 2015 And Operated on 26/12/2015, the year Jejunoileal intussusception. The primary diagnosis, therapeutic intervention, and outcomes: After physical examination and investigation, Hamartomatous polyp (P-J Secondary Intussuseception ) Conclusions: The following primary complaints were the reason for the patient's hospital admission. Upon entry to the hospital, the patient's main complaint was that Peutz Jegher Syndrome was identified as the patient's condition once all investigations were complete. The patient now needs appropriate medical attention and quality nursing care.

Alcohol-Related Liver Disease: An Overview on Pathophysiology, Diagnosis and Therapeutic Perspectives

Alcohol-related liver disease (ALD) refers to a spectrum of liver manifestations ranging from fatty liver diseases, steatohepatitis, and fibrosis/cirrhosis with chronic inflammation primarily due to excessive alcohol use. Currently, ALD is considered as one of the most prevalent causes of liver disease-associated mortality worldwide. Although the pathogenesis of ALD has been intensively investigated, the present understanding of its biomarkers in the context of early clinical diagnosis is not complete, and novel therapeutic targets that can significantly alleviate advanced forms of ALD are limited. While alcohol abstinence remains the primary therapeutic intervention for managing ALD, there are currently no approved medications for treating ALD. Furthermore, given the similarities and the differences between ALD and non-alcoholic fatty liver disease in terms of disease progression and underlying molecular mechanisms, numerous studies have demonstrated that many therapeutic interventions targeting several signaling pathways, including oxidative stress, inflammatory response, hormonal regulation, and hepatocyte death play a significant role in ALD treatment. Therefore, in this review, we summarized several key molecular targets and their modes of action in ALD progression. We also described the updated therapeutic options for ALD management with a particular emphasis on potentially novel signaling pathways.

881TiP NEOplus: A phase II study of neoadjuvant lenvatinib and pembrolizumab in resectable mucosal melanoma

Mucosal melanoma is a rare type of melanoma in the Caucasian population and a dominate subtype in Asia, which generally carries a worse prognosis than cutaneous melanoma. Surgery remains the primary therapeutic intervention for mucosal melanoma. Pembrolizumab showed modest objective response rate (ORR, 13%) in advanced mucosal melanoma in the Chinese population (NCT02628067). Recent study has also demonstrated neoadjuvant therapy with pembrolizumab could lead to pathological response which associated with reduced risk of recurrence and improved survival. Lenvatinib is also a kinase inhibitor that inhibits the kinase activities of VEGFR1,2, 3, which has been approved by the FDA for differentiated thyroid cancer, advanced renal cell carcinoma and hepatocellular carcinoma. This trial hypothesize that neoadjuvant combination of pembrolizumab and lenvatinib may enhance anti-tumor activity and prolong RFS and OS in resectable mucosal melanoma. NEOplus(NCT04622566) is a single-arm, open-label phase 2 trial evaluating the efficacy and safety of neoadjuvant with lenvatinib and pembrolizumab in resectable mucosal melanoma. Newly diagnosed resectable mucosal melanoma patients without any previous anti-cancer treatment may be included. Twenty-six patients will be enrolled in this study and will received pembrolizumab (200mg IV, Q3W) in combination with lenvatinib (20mg QD) for 6 weeks before surgery. Pembrolizumab (200mg IV, Q3W) will be as adjuvant treatment for 15 cycles until the disease progresses or intolerable toxicity. The primary endpoint is complete pathologic response (pCR), which is defined as no residual tumor cells in tumor bed or lymph nodes. Secondary endpoints are pathologic response which include pCR, MPR and pPR (MPR was defined as less than 10% of residual viable tumor cells. pPR was defined as less than 50% residual viable tumor cells); relapse-free survival (RFS), overall survival (OS) and safety etc. Enrollment began in Oct 2021. NCT04622566. The authors.

A Life-Threatening Incidence of Neurotoxic Indian Krait Snake Bite: A Case Report

The Indian Krait delivers one of the most lethal venoms compared to other Asian snakes. The venom of the common Krait comprises substantial neurotoxins that cause muscular paralysis. Significant snake bite incidence occurs in rural areas. The significant death rate caused by snake bites is seldomly reported in the medical literature. A 14-year-old adolescent girl was brought by her parents to the emergency department (ED) in an unconscious state. The patient reported swelling on her right hand with fang marks of a snake bite, sweating, and increased salivation. The primary therapeutic intervention was given to the patient and she was treated with intravenous anti-snake venom serum, antibiotics, and anti-epileptics during hospitalisation.

Functional and Synergistic Relationship of Pelvic Floor and Some Hip Joint Muscles

Background and Aims Pelvic Floor Muscle (PFM) training is the primary therapeutic intervention of PFM dysfunctions. In addition, strengthening some other muscles such as; Gluteus Maximus, Obturator Internus, Adductor Magnus, and D2 extension PNF pattern is suggested as complementary therapeutic methods. This study aimed to investigate the synergistic relationship between these muscles and PFM function using Transabdominal Ultrasonography and bladder base displacement. Methods Twenty-one healthy multiparous women, aged 20-40 years, participated in this cross-sectional and analytical study. Transabdominal Ultrasonography was used to measure the bladder base displacement. The following five different interventions were randomly performed, 1) PFM contraction, 2) Gluteus Maximus contraction, 3) Obturator Internus, 4) Adductor Magnus contraction, and 5) D2 extension PNF pattern. All participants did contractions three times with a 30 second rest period between each contraction. The mean of three measurements in each position was compared with the PFM contraction. Kolmogorov-Smirnov fitness test and Repeated Measures ANOVA were used to analyze the data. A level of P≤0.05 was considered significant. Results The main effect of all interventions was significant compared to the contraction of the PFM (P=0.0001 and F=392.9). The amount of the bladder wall base displacement during Obturator Internus contraction and PNF D2 Extensor Pattern was more significant than the PFM contraction and in the same direction. With the Gluteus Maximus muscle contraction, the bladder base displacement was more significant than the contraction of the PFM. Still, in the opposite direction, and with the contraction of the Adductor Magnus muscle, it was approximately equal to the contraction of the PFM (P≤0.0001). Conclusion This study showed that the contraction of Adductor Magnus, Obturator, pelvic floor muscles, and also the PNF D2 Extensor Pattern could increase the bladder base displacement, which could confirm the synergistic relationship between these muscles and the PFM. However, this relationship was not observed in Gluteus Maximus muscle contraction.

Cancer Models to Defeat Therapy Resistance in Pancreatic Ductal Adenocarcinoma

One of the largest hurdles to the efficacy of cancer therapeutics, and a main cause of relapse, is therapy resistance. In response, researchers have developed model systems to better understand therapy resistance. Cancer research employs several model systems that reflect the biology of actual human tumors: in vitro models (2D, 3D cell cultures), in vivo models (PDX, GEMMS, transgenic), proteomic models, and computational or mathematical models. One cancer that has been extensively modeled is pancreatic ductal adenocarcinoma (PDAC). PDAC is the third most common cause of annual cancer deaths in developed countries; as its incidence and mortality rates continue to increase, PDAC is projected to be the second leading cause of cancer deaths by 2030. Although chemotherapy is a pillar of clinical PDAC treatment, its outcome typically leads to multi-drug resistance, drastically restricting the curative effect of drugs for a variety of tumors. Elucidating the underlying mechanisms for resistance through different models is essential for the development of new strategies and therapies. This review provides insight into the range of in vitro and in vivo models of pancreatic cancer used in preclinical research. This paper provides an overview of platforms for cancer research with a focus on those devoted to resistance mechanisms in PDAC and to the primary therapeutic intervention for PDAC, gemcitabine (GEM).