The Effect of Intradermal Botulinum Toxin a injections on painful diabetic polyneuropathy.

BACKGROUND AND AIMS: Botulinum toxin type A (BTX-A) have been recently administered to improve Diabetic neuropathies; however, the efficacy of this treatment for relieving pain in painful diabetic polyneuropathy (DPN) has not been studied yet. Herein, we investigated the efficacy of botulinum toxin A (BTX-A) on DPN. METHODS: This prospective, randomized, double-blind, controlled trial was performed in Imam Hossein Medical Center, pain clinic (Tehran, Iran). Diabetic patients (141 cases), between 40 and 70 years old with polyneuropathy in lower limbs were randomly assigned to one of these three groups: 1. Group D1 received 150 units of BTX-A in one foot and normal saline 0.9% in the other foot, 2. Group D2 received BTX-A 150 units in both feet, 3. Group N received normal saline 0.9% in both feet. All injections were performed intradermally using insulin syringes in 20 different points of foot. Visual analogue scale (VAS) and neuropathy pain scale (NPS) were used to compare the groups. RESULTS: The improvement of VAS, pain intensity, sharp and hot sensation, sensitive and unpleasant sensation, deep and surface sensation was significant when comparing BTX-A and placebo groups. However, dull and cold sensations improvement (p = 0.114, and p = 0.653; respectively) did not show a significant difference between BTX-A injection and placebo groups. Furthermore, the percentage of changes after treatment indicated that sharp pain was improved more than other complaints (80%, 81%, and 37% for D1, D2, and N groups; respectively). CONCLUSION: Intradermal administration of BTX-A was effective in improving VAS and all of the items of NPS in patients with diabetic polyneuropathy, except for dull and cold sensation.

The fluctuation of APC gene in WNT signaling with adenine deletion of adenomatous polyposis coli, is associated in colorectal cancer / A flutuação do gene da APC na via de sinalização WNT com deleção de adenina na polipose adenomatosa do cólon está associada ao câncer colorretal

ABSTRACT Colorectal cancer is one of the most important malignancies in the classification of gastrointestinal cancers. One of the predisposing factors at molecular level for this cancer is via WNT signaling which is associated with the vast numbers of different genes. Thus, in this study, we aimed to investigate whether Adenomatous Polyposis Coli gene (APC) mutation of rs41115in two locations such as 132.002 and 131.989 acts as a trigger or cause of colorectal cancer. Relatively, 30 blood samples of colorectal cancer patients and 30 normal blood samples as control group after colonoscopy and also confirmation of pathology report at Rohani Hospital in Babol (Iran) were investigated. The primers were designed in order to be included the rs41115 to identify the particular polymorphisms of gene. The polymerase chain reaction (PCR direct sequencing method) was used. Conclusively, deletion of adenine in two specific locations such as 131.989 and 132.002 has been identified, but there was no relationship between rs41115 polymorphisms located in adenomatous polyposis coli gene and colorectal cancer.

RESUMO O câncer colorretal é uma das neoplasias malignas mais importantes na classificação dos cânceres gastrointestinais. Um dos fatores predisponentes no âmbito molecular para esse câncer é através da via de sinalização WNT, que está associada a um grande número de genes diferentes. Portanto, neste estudo, objetivamos investigar se a mutação rs41115 do gene da polipose adenomatosa do cólon (Adenomatous Polyposis Coli - APC) em dois locais como 132.002 e 131.989 atua como gatilho ou como causa do câncer colorretal. Relativamente, 30 amostras de sangue de pacientes com câncer colorretal e 30 amostras de sangue normal (grupo controle) foram analisadas após a colonoscopia, bem como a confirmação do laudo da patologia no Rohani Hospital em Babol (Irã). Os primers foram projetados de modo a incluir o rs41115 para identificar os polimorfismos particulares do gene. A reação em cadeia da polimerase (método de sequenciamento direto por PCR) foi utilizada. Conclusivamente, a deleção de adenina em dois locais específicos, como 131.989 e 132.002, foi identificada, mas não houve relação entre o polimorfismo rs41115 localizado no gene da polipose adenomatosa do cólon e o câncer colorretal.

Comparison of Hemodynamic Stability and Pain Control in Lateral and Prone Positions in Patients Undergoing Percutaneous Nephrolithotomy: A Randomized Controlled Trial.

PURPOSE: Percutaneous nephrolithotomy (PCNL) is the preferred surgical treatment in many cases of kidney stones which is performed in different positions such as prone, lateral, and supine. This study was designed to evaluate whether patient position (lateral versus . prone) has an effect on the need for analgesia and onset of pain after surgery. MATERIALS AND METHODS: Patient with confirmed kidney stones (size ? 2 cm) who were candidates for PCNL were enrolled in this study. The required biochemical analyses were performed preoperatively. All patients  underwent spinal anesthesia by the same anesthesiologists and then were randomly divided into two separate groups as lateral (L) and prone (P) positions. The operations' start and end time, required time for proper access into target calyces, additional need for analgesic or cardiac drugs, duration of analgesia, and onset of pain after PCNL were carefully recorded and then compared between the two groups. RESULTS: In total, 51 patients were evaluated of whom 39 were men and 12 were women. Mean duration of analgesia after PCNL surgery in P group (173 ± 8 min) was significantly longer than in L group (147±12 min) (P = .001). Furthermore, the amount of ephedrine usage in L group (3.6 ± 1.5mg) was significantly lower than in the P group (16.4 ± 12mg), suggesting more hemodynamic variations in the P group during the operation. CONCLUSION: Our randomized control trial study shows that choosing the optimal position in the PCNL technique depends on  patient's condition. If hemodynamic control is of matter to the anesthesiologist, then lateral position is more appropriate. However, if control of pain and longer time of analgesia are important,  prone position may be preferred.

Antigen delivery format variation and formulation stability through use of a hybrid vector.

A hybrid biological-biomaterial antigen delivery vector comprised of a polymeric shell encapsulating an Escherichia coli core was previously developed for in situ antigen production and subsequent delivery. Due to the engineering capacity of the bacterial core, the hybrid vector provides unique opportunities for immunogenicity optimization through varying cellular localization (cytoplasm, periplasm, cellular surface) and type (protein or DNA) of antigen. In this work, three protein-based hybrid vector formats were compared in which the pneumococcal surface protein A (PspA) was localized to the cytoplasm, surface, and periplasmic space of the bacterial core for vaccination against pneumococcal disease. Furthermore, we tested the hybrid vector's capacity as a DNA vaccine against Streptococcus pneumoniae by introducing a plasmid into the bacterial core to facilitate PspA expression in antigen presenting cells (APCs). Through testing these various formulations, we determined that cytoplasmic accumulation of PspA elicited the strongest immune response (antibody production and protection against bacterial challenge) and enabled complete protection at substantially lower doses when compared to vaccination with PspA + adjuvant. We also improved the storage stability of the hybrid vector to retain complete activity after 1 month at 4 °C using an approach in which hybrid vectors suspended in a microbial freeze drying buffer were desiccated. These results demonstrate the flexibility and robustness of the hybrid vector formulation, which has the potential to be a potent vaccine against S. pneumoniae.

Cancer signaling pathways with a therapeutic approach: An overview in epigenetic regulations of cancer stem cells.

One of the most important issues in cancer progression is caner stem cells (CSCs) which have illustrated that the bulk tumors can arise from a special combination of cells. Remarkably, it has been proposed to be a notable and strong factor in carcinogenesis and tumorogenesis and also is a key parameter of therapeutic resistance. In this way, recent findings have shown the key roles of epigenetic regulations in cancer development.Considerably, epigenetic regulations of gene expression is an active and dynamic process including histone modification, DNA methylation and chromatin remodeling with a reversible trait.Meaningly, recent and novel findings have described the significance of epigenetic regulatory proteins from divers features comprising tumorogenesis,stem cell proliferation and carcinogenesis. Evidently, abnormal epigenetic regulations is directly related with many serious disorders particularly different cancers. We here review a discussion of how the deregulation of eclectic pathways containing Sonic Hedgehog (SHH), WNT, Beta catenin and NOTCH can help to carcinogenesis specially focusing to survival and maintenance of CSCs in therapeutic approach.

Anesthesia Management of Vitrectomy in a Patient with Sturge-Weber Syndrome.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder, characterized by leptomeningeal angiomas involving the oral cavity, trachea, larynx, and face. Herein, we present a case of vitrectomy in a seven-year-old boy with SWS. The patient showed hemangioma on the left side of his face, as well as mental retardation and epilepsy. Preoperative examination revealed no apparent hemangioma in the oral cavity, pharynx, larynx, or trachea. However, he was predicted to have difficult airway intubation, as the oral cavity was smaller than the normal size. The minimum Mallampati score was 3-4 due to macroglossia. First, we applied awake intubation, but he failed to follow the commands. We proceeded to general anesthesia with propofol and did not use any muscle relaxants to maintain spontaneous breathing. A laryngeal mask airway was inserted to minimize any harm to possible oral angiomas. The patient was hemodynamically stable and extubated without any complications, such as bleeding or respiratory problems.

Three-dimensional Printing and Augmented Reality: Enhanced Precision for Robotic Assisted Partial Nephrectomy.

OBJECTIVE: To describe novel 3-dimensional (3D) printing and augmented reality (AR) methods of image data visualization to facilitate anatomic understanding and to assist with surgical planning and decision-making during robotic partial nephrectomy. MATERIALS AND METHODS: We created a video of the workflow for creating 3D printed and AR kidney models along with their application to robotic partial nephrectomy. Key steps in their development are (1) radiology examination (magnetic resonance imaging and computed tomography), (2) image segmentation, (3) preparing for 3D printing or AR, and (4) printing the model or deploying the model to the AR device. RESULTS: We demonstrate the workflow and utility of 3D printing and AR kidney models applied to a case of a 70-year-old woman with a 3.4 cm renal mass on her left pelvic kidney. A 3D printed kidney model was created using multicolor PolyJet technology (Stratasys J750), allowing a transparent kidney with coloring of the renal tumor, artery, vein, and ureter. An AR kidney model was created using Unity 3D software and deployed to a Microsoft HoloLens. The 3D printed and AR models were used preoperatively and intraoperatively to assist in robotic partial nephrectomy. To date, we have created 15 3D printed and AR kidney models to use for robotic partial nephrectomy planning and intraoperative guidance. The application of 3D printed and AR models is safe and feasible and can influence surgical decisions. CONCLUSION: Our video highlights the workflow and novel application of 3D printed and AR kidney models to provide preoperative guidance for robotic partial nephrectomy. The insights gained from advanced visualization can influence surgical planning decisions.

Comprehensive vaccine design for commensal disease progression.

Commensal organisms with the potential to cause disease pose a challenge in developing treatment options. Using the example featured in this study, pneumococcal disease begins with Streptococcus pneumoniae colonization, followed by triggering events that prompt the release of a virulent subpopulation of bacteria. Current vaccines focus on colonization prevention, which poses unintended consequences of serotype niche replacement. In this study, noncovalent colocalization of two classes of complementary antigens, one to prevent the colonization of the most aggressive S. pneumoniae serotypes and another to restrict virulence transition, provides complete vaccine effectiveness in animal subjects and the most comprehensive coverage of disease reported to date. As a result, the proposed vaccine formulation offers universal pneumococcal disease prevention with the prospect of effectively managing a disease that afflicts tens to hundreds of millions globally. The approach more generally puts forth a balanced prophylactic treatment strategy in response to complex commensal-host dynamics.

Pressing diseases that represent promising targets for gene therapy.

Over time, there has been a growing interest in the application of gene therapy within the healthcare industry as demonstrated by the nearly 3,000 clinical trials associated with gene therapy that are listed in clinicaltrials.gov. However, there are various difficulties associated with gene therapy that have limited the realization of licensed gene therapies to only a handful of treatments. Furthermore, efforts to develop gene therapeutics have been narrowly focused and most clinical trials have sought to develop treatments for cancer (64.6%), monogenic diseases (10.5%), infectious diseases (7.4%), and cardiovascular diseases (7.4%). In addition, nearly 70% of clinical trials have utilized viral-based delivery systems, despite various concerns associated with this strategy. Each of these factors highlights the lack of diversity in the development of gene therapeutics that should be addressed. In recent years, developments in gene manipulation and delivery such as CRISPR and non-viral vectors (e.g., liposomes) demonstrate promise for improving outcomes for gene therapy. The increased fidelity and capacity afforded by these technologies provide the potential to improve upon contemporary gene therapy approaches and enable the development of treatments for less-emphasized disorders. In this review, we provide a summary of gene delivery technology and discuss various developments in gene therapy technology. We conclude by proposing several genetic conditions that represent promising targets for gene therapy given recent developments in gene delivery and manipulation.

Brain metastasis in breast cancer: a comprehensive literature review.

This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER-, 36 % progesterone receptor (PR)+, 34 % PR-, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2-, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the following: whole brain radiation therapy (52 %), chemotherapy (51 %), stereotactic radiosurgery (20 %), surgical resection (14 %), trastuzumab (39 %) for HER2 positive tumors, and hormonal therapy (34 %) for ER and/or PR positive tumors. Factors that had an impact on prognosis included grade and size of the tumor, multiple metastases, presence of extra-cranial metastasis, triple negative or HER2+ biomarker status, and high Karnovsky score. Novel therapies such as application of agents to reduce tumor angiogenesis or alter permeability of the blood brain barrier are being explored with preliminary results suggesting a potential to improve survival after brain metastasis. Other potential therapies based on genetic alterations in the tumor and the microenvironment in the brain are being investigated; these are briefly discussed.

Causes of visual impairment among patients referred to a visual rehabilitation clinic in Iran.

PURPOSE: Epidemiologic evaluation and investigating the causes of visual impairment in any society is a matter of concern and has a direct effect on the country's health care planning. In this study we describe causes of low vision and blindness in Iranian patients referred to rehabilitation clinics for taking vision aids. METHODS: In this cross-sectional study, visual acuity was classified based on best-corrected visual acuity in the better eye according to the World Health Organization definition (blindness, visual acuity [VA] < 20 / 400; severe visual impairment, VA < 20 / 200-20 / 400; mild to moderate visual impairment, VA < 20 / 60-20 / 200). The causes of blindness and low vision were determined using the 10th version of International Classification of Diseases based on the main cause in both eyes. To describe data, we used mean ± SD and frequency. RESULTS: The study included 432 patients, 65% male, with a mean age of 43.6 ± 25.5 years (range, 3 to 92 years). Mild to moderate visual impairment, severe visual impairment and blindness were present in 122 (28.8%), 196 (46.4%) and 105 (24.8%) of the patients, respectively. The main causes of visual impairment were retinal and choroidal diseases (74.5%), optic nerve and optic tract diseases (9.8%), vitreous and globe disorders (5.3%), congenital cataract (3.1%), and glaucoma (2.6%). The distribution pattern of the causes was similar in all age subgroups. CONCLUSIONS: Diseases of the retina and choroid are the main cause of visual impairment among patients referred to an academic visual rehabilitation clinic in Iran.

Association between acute corneal hydrops in patients with keratoconus and mitral valve prolapse.

PURPOSE: To investigate the association between corneal hydrops in patients with keratoconus (KCN) and mitral valve prolapse (MVP). METHODS: This case-control study included patients with KCN with corneal hydrops who were referred to Labbafinejad Medical Center or a private clinic between March 2006 and March 2008, as the case group. The control group included group-matched individuals who were selected from patients of the same medical centers without any ophthalmic diseases. The size of the control group was 4 times that of the case group to increase the power of the study. All subjects were referred for cardiac examination and underwent 2-dimensional, M-mode, and color Doppler echocardiography. The criteria of Perloff et al were used for diagnosis of MVP. Fisher exact test and logistic regression analysis were used to compare these 2 groups. RESULTS: Overall, 160 participants (32 cases and 128 controls) with mean age of 31.0 ± 13.2 years were studied. Prevalence of MVP was 65.6% in the case group and 9% in controls (P < 0.001). Patients with hydrops had an odds ratio of 26.7 for having MVP (95% confidence interval, 9.5-75.2). Age- and sex-adjusted analyses revealed that the odds ratio of MVP in the case group was higher than that in the control group. CONCLUSIONS: There seems to be a correlation between corneal hydrops secondary to KCN and MVP, suggesting further evaluation to assess mitral valve status.