Hyperhidrosis: Anatomy,Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent.     

Assessment of women's empowerment: An exploratory study to develop a valid and reliable Persian-version tool

Abstract

Lack of a valid and reliable women's empowerment tool was reported by previous studies in Iran. The authors of this paper, accordingly, intended to fill this gap by developing a valid questionnaire. 600 women in Dezful city, southeast of Iran, took part in the study in 2014–2015. Multistage sampling method was used to recruit the participants. Our exploratory factor analysis revealed that 18 items of the model loaded on 4 factors. Internal consistency of the questionnaire was suitable as Cronbach's alpha coefficient was 0.77. Considering high validity and shortness of the questionnaire, it can be used as a trustful and comprehensive tool to measure women's empowerment in future studies.     

The role of the tumor microenvironment in colorectal cancer and the potential therapeutic approaches

BackgroundColorectal cancer (CRC) with a high prevalence is recognized as the fourth most common cause of cancer‐related death globally. Over the past decade, there has been growing interest in the network of tumor cells, stromal cells, immune cells, blood vessel cells, and fibroblasts that comprise the tumor microenvironment (TME) to identify new therapeutic interventions.MethodsDatabases, such as Google Scholar, PubMed, and Scopus, were searched to provide an overview of the recent research progress related to targeting the TME as a novel therapeutic approach.ResultsTumor microenvironment as a result of the cross talk between these cells may result in either advantages or disadvantages in tumor development and metastasis, affecting the signals and responses from the surrounding cells. Whilst chemotherapy has led to an improvement in CRC patients'' survival, the metastatic aspect of the disease remains difficult to avoid.ConclusionsThe present review emphasizes the structure and function of the TME, alterations in the TME, its role in the incidence and progression of CRC, the effects on tumor development and metastasis, and also the potential of its alterations as therapeutic targets. It should be noted that providing novel studies in this field of research might help us to achieve practical therapeutic strategies based on their interaction.     

Bromodomain inhibition overcomes treatment resistance in distinct molecular subtypes of melanoma

Therapy of BRAF-mutant melanoma with selective inhibitors of BRAF (BRAFi) and MEK (MEKi) represents a major clinical advance but acquired resistance to therapy has emerged as a key obstacle. To date, no clinical approaches successfully resensitize to BRAF/MEK inhibition. Here, we develop a therapeutic strategy for melanoma using bromosporine, a bromodomain inhibitor. Bromosporine (bromo) monotherapy produced significant anti-tumor effects against established melanoma cell lines and patient-derived xenografts (PDXs). Combinatorial therapy involving bromosporine and cobimetinib (bromo/cobi) showed synergistic anti-tumor effects in multiple BRAFi-resistant PDX models. The bromo/cobi combination was superior in vivo to standard BRAFi/MEKi therapy in the treatment-naive BRAF-mutant setting and to MEKi alone in the setting of immunotherapy-resistant NRAS- and NF1-mutant melanoma. RNA sequencing of xenografts treated with bromo/cobi revealed profound down-regulation of genes critical to cell division and mitotic progression. Bromo/cobi treatment resulted in marked DNA damage and cell-cycle arrest, resulting in induction of apoptosis. These studies introduce bromodomain inhibition, alone or combined with agents targeting the mitogen activated protein kinase pathway, as a rational therapeutic approach for melanoma refractory to standard targeted or immunotherapeutic approaches.

Melanoma is the fifth most common malignancy in the Unites States, with an estimated 106,110 new cases in 2021 (1). The death toll attributed to melanoma has decreased sharply, owing in part to the revolution that has taken place in the therapy of advanced disease, with significant advances both in immunotherapeutic and targeted interventions. In the realm of targeted therapy, the efficacy of small molecule inhibitors targeting mutant BRAF in metastatic melanoma (2, 3) represented a landmark in the targeted therapy of cancer. Subsequently, the combination of BRAF and MEK inhibition resulted in increased response rates and prolonged survival (4–6). More recently, durable responses have been reported with BRAF/MEK-targeted therapy (7). However, despite these clear improvements in patient outcome, many patients eventually progress. As a result, the development of acquired resistance to targeted agents constitutes a significant clinical obstacle. While numerous mechanisms of resistance to targeted therapy have been described (8), many of these mechanisms result in reactivation of the mitogen activated protein kinase (MAPK) pathway in which BRAF operates (9, 10). Therefore, new therapeutic approaches will be required to increase the proportion of responding patients, the durability of the responses observed, and to resensitize melanoma cells to BRAF inhibitors upon the development of acquired resistance. To date, few effective targets for combinatorial therapy with BRAF inhibitors (beyond MEK) have been identified, and none that have proved superior to the BRAFi/MEKi combination.Previously, we identified an important role for the BPTF gene in melanoma progression, and as a potential therapeutic target (11). BPTF promotes melanoma progression by activating a cascade of gene expression including ERK, BCL2, and BCL-XL, resulting in promotion of cell-cycle progression and suppression of apoptosis. BPTF gene silencing resulted in abrogation of the proliferative and metastatic potential of melanoma cells and in sensitization to BRAF inhibition (11).Recently, bromodomain inhibition has emerged as a novel approach to cancer therapy. Bromodomains are protein motifs that bind to acetylated lysine residues on histones, with a critical role in chromatin remodeling (12, 13). The development of ligands targeting the BET (bromodomain and extracellular-terminal) family member BRD4 (14) demonstrated the potential of small molecule inhibition of the bromodomain-acetyl-lysine interaction and is being pursued actively in the clinical arena. However, BET family bromodomains do not share significant sequence homology with that of BPTF (15), indicating that distinct inhibitors will be required to effectively target BPTF. Collectively, these observations suggest the potential utility of a bromodomain inhibitor, alone or in combination with MAPK pathway inhibition, as a rational therapeutic strategy for melanoma, which represents the focus of the current analysis.     

COVID‐19‐associated mucormycosis involving the maxilla

It is important to increase the awareness and knowledge of head and neck surgeons about the recent surge of craniofacial mucormycosis in COVID‐19 patients because early diagnosis and appropriate treatment are essential to improve the outcomes. Here, we describe clinical features, treatment protocols, and outcomes of treatment in eight patients with COVID‐19‐associated mucormycosis in the maxilla. Consistent with the findings of previous studies, our experience in the management of these eight patients shows that early administration of amphotericin B and prompt aggressive surgery are essential for optimal control of the disease.     

Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by immunohistochemistry

Odontogenic cysts are common lesions with different biological behavior. Odontogenic keratocysts (OKCs) and calcifying odontogenic cysts (COCs) with ameloblastoma-like epithelium are more aggressive than dentigerous cysts (DCs) and radicular cysts (RCs). Therefore, they were included in the list of odontogenic tumors by WHO. Osteopontin (OPN) is a calcium-binding glycoprotein present in many normal tissues. It plays a role in the migration and invasion of transformed epithelial cells. Binding of OPN to its receptor CD44v6 can enhance cell motility and migration. The purpose of this study was to compare the expression of these markers between odontogenic cysts of varying biological behavior. We examined OPN and CD44v6 expression in tissue sections of 14OKCs, 14COCs, 14RCs and 14DCs by immunohistochemistry. OPN and CD44v6 immunostaining was observed in all lining epithelial cells of the studied lesions with different degrees. The highest level of OPN and CD44v6 expression was found in OKCs, followed by COCs, RCs and DCs. Comparison of both markers among four groups revealed significant differences (P<0.001). Our findings suggest that higher level of OPN and CD44v6 expression in epithelial cells of some lesions such as OKC and COC can explain the local aggressive behavior of them.     

American Orthopaedic Foot and Ankle Society ankle–hindfoot scale: A cross-cultural adaptation and validation study from Iran

Background

The use of valid and reliable outcome rating scales is essential for evaluating the result of different treatments and interventions. The purposes of this study were to translate and culturally adapt the American Orthopaedic Foot and Ankle Society ankle–hindfoot scale (AOFAS-AHFS) into Persian languages and evaluate its psychometric properties.

Effects of education and experience on detection of proximal caries on digital radiographs

Objectives

Early detection of proximal caries can result in less-invasive treatments. This study aimed to assess the effects of education and experience on accurate detection of proximal caries on digital radiographs.

Methods

Third-year and sixth-year dental students, maxillofacial radiology postgraduate students, and general dentists comprised the study population (total, 28). Standard digital bitewing radiographs were obtained for 50 extracted teeth, and evaluated for proximal caries on a monitor. All assessments were performed under ambient light (<50 lux). The teeth were subsequently sectioned into 1-mm-thick slices. After reaching the lesion, it was visually inspected, and then determined for its depth in each slice using a caries detector solution. A four-scale grading system for assessment of lesion depth. These results were considered to be the gold standard, and compared with the opinions of the observers. Data were analyzed using SPSS16 software for kappa, sensitivity, specificity, false-negative, false-positive, negative predictive value, and positive predictive value statistics. The kappa coefficients were used to compare the accuracy of diagnoses of the observers and the extents of involvement of tooth structures.

Results

The diagnostic accuracy for grade I caries was 21.9 % among third-year dental students, 17.4 % among sixth-year dental students, 34.5 % among maxillofacial radiology postgraduate students, and 14.3 % among general dentists. The respective diagnostic accuracies were 16.2, 15.2, 5.7, and 7.6 % for grade II caries and 3.5, 32.1, 25, and 14.2 % for grade III caries.

Conclusions

Although education played a great role in improving caries detection skill, it failed to raise it to an acceptable range.

     

High expression of CEACAM19, a new member of carcinoembryonic antigen gene family,in patients with breast cancer

Carcinoembryonic antigen (CEA) family members play important roles in malignancies and are introduced as biomarkers in different types of cancers. Among them CEACAM19 (CEAL1) gene, a new member of the CEA family, remains to be fully elucidated. The aim of this study was investigating the mRNA expression level of CEACAM19 in tumor samples of breast cancer patients compared to breast tissue of normal individuals. We evaluated the expression level of this gene in 75 breast tumors by using real-time quantitative PCR. Also, we studied the correlation between CEACAM19 expression and clinicopathological features and hormone receptors status, including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 of patients. Out of the enrolled patients, six of them (7.9%) showed low expression, ten (13.2%) showed normal expression and 59 (77.6%) showed high expression of CEACAM19. There was a significant correlation between high expression of CEACAM19 gene in tumor samples compared to normal tissues (P = 0.039). No significant correlation was seen between clinicopathological factors and disease-free survival with mRNA levels of CEACAM19 in tumor samples, while the difference between the expression of CEACAM19 in ER/PR-positive and ER/PR-negative breast cancer patients was statistically significant (P = 0.046). In conclusion, CEACAM19 showed high expression in tumor samples compared to normal mammary tissue. In addition, CEACAM19 may represent as a novel therapeutic target in certain subgroups of breast cancer patients such as ER/PR-negative. Critical roles of CEA proteins in tumor progression may nominate them as robust potential targets for therapeutic intervention in near future.