Due to unknown safety concerns, sugammadex should not be administered to patients withend-stage renal disease (ESRD). However, because the supply of benzylisoquinolinium-typeneuromuscular blocking agents (NMBAs) has been discontinued, rocuronium is the onlynon-depolarizing NMBA that can be used in clinical settings in some countries, includingSouth Korea. The administration of sugammadex cannot be avoided to achieve rapid andcomplete neuromuscular recovery in patients with ESRD or renal transplantation after rocuronium administration. Although there has been a limited number of clinical studies involving the use of sugammadex in patients with ESRD, studies have shown that sugammadexcan effectively and safely reverse rocuronium-induced neuromuscular blockade (NMB) inpatients with ESRD, however recovery of neuromuscular function in patients with ESRD isslower than in patients with normal renal function. Nonetheless, safety-concerns are yet tobe addressed. Considering the small number of clinical studies, high heterogeneity amongstudies, and insufficient safety information, more extensive data on the efficacy and safetyof sugammadex in patients with ESRD are needed. In particular, it is important to securedata on safety, including residual NMB after surgery, recurarization and cardiorespiratorycomplications, anaphylactic reactions, and long-term morbidity and mortality. Furthermore,anesthesiologists should remember that performing proper quantitative neuromuscularmonitoring and neuromuscular management based on the monitoring signs are the mostessential requirements when using sugammadex in patients with ESRD.

Major depressive disorder is a leading global cause of disability. There is a growing interest for memory in mood disorders since it might constitute an original tool for prevention, diagnosis, and treatment. MDD is associated with impaired autobiographical memory characterized by a tendency to overgeneral memory, rather than vivid episodic self-defining memory, which is mandatory for problem-solving and projection in the future. This memory bias is maintained by three mechanisms: ruminations, avoidance, and impaired executive control. If we adopt a broader and comprehensive perspective, we can hypothesize that all those alterations have the potential to impair self-identity updating. We posit that this update requires a double referencing process: (1) to internalized self-representation and (2) to an externalized framework dealing with the representation of the consequence of actions. Diagnostic and therapeutic implications are discussed in the light of this model and the importance of assessing autobiographical memory in MDD is highlighted. This article is categorized under: Psychology > Memory Psychology > Brain Function and Dysfunction Neuroscience > Clinical.

Cellular senescence is a complex process involving a close-to-irreversible arrest of the cell cycle, the acquisition of the senescence-associated secretory phenotype (SASP), as well as profound changes in the expression of cell surface proteins that determine the recognition of senescent cells by innate and cognate immune effectors including macrophages, NK, NKT and T cells. It is important to note that senescence can occur in a transient fashion to improve the homeostatic response of tissues to stress. Moreover, both the excessive generation and the insufficient elimination of senescent cells may contribute to pathological aging. Attempts are being made to identify the mechanisms through which senescent cell avoid their destruction by immune effectors. Such mechanisms involve the cell surface expression of immunosuppressive molecules including PD-L1 and PD-L2 to ligate PD-1 on T cells, as well as tolerogenic MHC class-I variants. In addition, senescent cells can secrete factors that attract immunosuppressive and pro-inflammatory cells into the microenvironment. Each of these immune evasion mechanism offers a target for therapeutic intervention, e.g., by blocking the interaction between PD-1 and PD-L1 or PD-L2, upregulating immunogenic MHC class-I molecules and eliminating immunosuppressive cell types. In addition, senescent cells differ in their antigenic makeup and immunopeptidome from their normal counterparts, hence offering the opportunity to stimulate immune response against senescence-associated antigens. Ideally, immunological anti-senescence strategies should succeed in selectively eliminating pathogenic senescent cells but spare homeostatic senescence.

Chronic obstructive pulmonary disease is a kind of chronic lung disease characterized by persistent air flow obstruction, which was the third leading cause of death in China. The incidence of COPD is steadily and increasing and has been a globally sever disease. Accordingly, it is urgently needed to explore how to diagnose and treat COPD timely. This study aims to find key genes to diagnose COPD as soon as possible to avoid COPD processing and analyze immune cell infiltration between COPD early stage and late stage. Two GEO datasets were merged as the merge data for analyses. 157 DEGs were used for GSEA analysis to find the pathway between COPD early stage and late stage. Above all, gene EXPH5 stood out from the screen as the most likely candidate diagnosis biomarker of COPD indicating the late-stage by least LASSO and SVM-RFE. ROC curves of EXPH5 were applied to represent the discriminatory ability through the area under the curve which is the gold standard to evaluate the accuracy of diagnosis and survival rate. The CIBERSORT algorithm was used to assess the distribution of tissue-infiltrating immune cells between two COPD stages. The diagnosis biomarker, gene EXPH5 had a positive correlation with NK cells resting; mast cell resting, eosinophils, and negative correlation with T cell gamma delta, macrophages M1, which underscore the role of gene and immune cell infiltration. To make results more reliable, we further analyzed the gene EXPH5 expression in single-cell transcriptome data and showed again that EXPH5 genes significantly downregulated in the late stage of COPD especially in the main lung cell types AT1 and AT2. In a word, our study identified genes EXPH5 as a marker gene, which adds to the knowledge for clinical diagnosis and pharmaceutical design of COPD.

Asp-Glu-Ala-Asp (DEAD) box helicase 3 X-linked (DDX3X) plays important regulatory roles in the replication of many viruses. However, the role of DDX3X in rhabdovirus replication has seldomly been investigated. In this study, snakehead vesiculovirus (SHVV), a kind of fish rhabdovirus, was used to study the role of DDX3X in rhabdovirus replication. DDX3X was identified as an interacting partner of SHVV phosphoprotein (P). The expression level of DDX3X was increased at an early stage of SHVV infection and then decreased to a normal level at a later infection stage. Overexpression of DDX3X promoted, while knockdown of DDX3X using specific small interfering RNAs (siRNAs) suppressed, SHVV replication, indicating that DDX3X was a proviral factor for SHVV replication. The N-terminal and core domains of DDX3X (DDX3X-N and DDX3X-Core) were determined to be the regions responsible for its interaction with SHVV P. Overexpression of DDX3X-Core suppressed SHVV replication by competitively disrupting the interaction between full-length DDX3X and SHVV P, suggesting that full-length DDX3X-P interaction was required for SHVV replication. Mechanistically, DDX3X-mediated promotion of SHVV replication was due not to inhibition of interferon expression but to maintenance of the stability of SHVV P to avoid autophagy-lysosome-dependent degradation. Collectively, our data suggest that DDX3X is hijacked by SHVV P to ensure effective replication of SHVV, which suggests an important anti-SHVV target. This study will help elucidate the role of DDX3X in regulating the replication of rhabdoviruses. IMPORTANCE Growing evidence has suggested that DDX3X plays important roles in virus replication. In one respect, DDX3X inhibits the replication of viruses, including hepatitis B virus, influenza A virus, Newcastle disease virus, duck Tembusu virus, and red-spotted grouper nervous necrosis virus. In another respect, DDX3X is required for the replication of viruses, including hepatitis C virus, Japanese encephalitis virus, West Nile virus, murine norovirus, herpes simplex virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because DDX3X has rarely been investigated in rhabdovirus replication, this study aimed at investigating the role of DDX3X in rhabdovirus replication by using the fish rhabdovirus SHVV as a model. We found that DDX3X was required for SHVV replication, with the mechanism that DDX3X interacts with and maintains the stability of SHVV phosphoprotein. Our data provide novel insights into the role of DDX3X in virus replication and will facilitate the design of antiviral drugs against rhabdovirus infection.

Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function and treatments aiming at stabilizing or slowing its progression may avoid or delay the necessity of kidney replacement therapy and the increased mortality associated with reduced kidney function. Metabolic acidosis, and less severe stages of the acid stress continuum, are common consequences of CKD and some interventional studies support that its correction slows the progression to end-stage kidney disease. This correction can be achieved with mineral alkali in the form of bicarbonate or citrate salts, ingestion of diets with fewer acid-producing food components or more base-producing food components, or a pharmacological approach. In this mini-review article, we summarize the potential mechanisms involved in the beneficial effects of alkali therapy. We also discuss the perspectives in the field and challenges that must be overcome to advance our understanding of such mechanisms.

Hereditary Angioedema (HAE) attacks show an increase in frequency and severity for pregnant and lactating females secondary to the hormonal changes. The diagnosis and management of HAE in pregnant and lactating females imposes a challenge for physicians due to the rarity of the disease and the paucity of the data for specific management.

Immune checkpoint inhibitors (ICIs) deeply changed the treatment landscape of breast cancer (BC). In particular, anti-programmed-death (ligand) 1 antibodies were approved for the treatment of triple-negative breast cancer (TNBC), both in first line for metastatic disease and in neoadjuvant setting, on the basis of a demonstrated improvement of the survival outcomes. In light of these results, current clinical trials aim at improving this benefit investigating novel combinations and strategies, at exploring the role of ICIs beyond TNBC, and at better selecting the patients in order to spare non-responders from avoidable toxicities. This narrative review aims at summarizing and discussing the evolving landscape of immunotherapeutic treatments for BC, highlighting the current challenges and the future perspectives.

Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription.

Stuttering is a puzzling disorder which involves voluntary repetition, prolongation along with blocking and other interruptions to the flow of speech. Stuttering impacts on quality of life of individuals with difficulties in overall social behavior and performance. The present study focuses on perception of stuttering by individual with stuttering and their experiences toward their stuttering among family and society. The present study was carried out in two phases. Phase 1 included the development of questionnaire and phase 2 incorporated the administration of questionnaire and analysis of the results. Total of 20 participants (16 males and 4 females) between the age ranges of 15-50 years (SD = 8.33) were included in the study. The results of present study consisted of perception of the individual with stuttering, their family members and other people regarding the probable cause, effects and treatment of stuttering. The causes were than categorized into psychological, superstitious, genetic, physiological and unknown. Likewise the treatment was categorized into speech therapy, medical treatment, self management strategies, superstitious beliefs and unknown. Many of the participants, their family members and other people had inappropriate, irrational and superstitious believes about the cause and treatment of stuttering due to which they faced many difficulties in their life. Hence from this study we conclude that there is requirement of awareness regarding the etiologies of stuttering and its consequences in hazarding the quality of life. It was also observed the urgent need of awareness regarding the speech therapy and its beneficial outcome in enhancing the fluency of individuals with stuttering, therefore, avoiding the consequence of the condition in their life.

Osteitis fibrosa cystica (OFC) is a skeletal disease related to long standing, end-stage hyperparathyroidism. However, nowadays hypercalcemia due to primary or secondary hyperparathyroidism can often be detected early by laboratory screening and imaging modalities; consequentially the frequency of osteitis fibrosa cystica has drastically declined. OFC, also termed as Brown tumor, can mimic primary bone tumors clinically, which often leads to misdiagnosis and inappropriate management. Moreover due to its rarity, it is usually not considered initially in the differential diagnosis of bony tumors. Case presentation: This is the case of a 19-year-old female, who presented with pain over the left ankle region for 3 months. The biochemical screening revealed a picture consistent with primary hyperparathyroidism and the radiologically proven to be left inferior parathyroid adenoma. She underwent excision of the primary parathyroid adenoma, and gradual regression of symptoms was noted postoperatively. Osteitis fibrosa cystica is a rare manifestation of hyperparathtyroidism, which has become a forgotten entity lately due to early identification of hypercalcaemia by modern techniques. A delay in the diagnosis of parathyroid adenoma results in manifestations that can be avoided. The diagnosis of OFC requires a high degree of clinical suspicion. When hypersecretion of PTH is corrected, spontaneous regression of the lesion is expected.

OSMF is a precancerous condition of the oral cavity. Cons umption of Areca nut in quid has been proved to be the most consistent factor. To assess middle ear function in OSMF patients by audiometry and tympanometry. Two Hundred patients of < 40 years of age with OSMF were examined and followed by PTA and impedance audiometry. Impaired mobility was seen in 20(10%) ears, and retraction of tympanic membrane was found in 36(18%) ears. Clinical staging was done in four stages. Majority of the patients were males (58%) in the age group of 21-30 years belonging to stage III (38%) and IV (26%) respectively. PTA showed varying degrees of hearing loss in 73 (36.5%) ears. In Grade I, mild hearing loss was seen in 10 (35.71%) ears and moderately severe hearing loss was in 5 (11.36%) ears whereas in Grade II mild hearing loss in 11(25%) ears. Grade III and IV showed mild hearing loss in 11(14.47%) and 12 (23.07%) respectively. Tympanometry revealed type A curve in 126 (63%) ears followed by C curve in 50 (25%) and B curve in 24 (12%) ears. In patients of OSMF, there is involvement of palatal/paratubal muscles in the fibrosis process, which causes eustachian tube malfunction leading to disturbed middle ear functions and negative middle ear pressure. Most patients of oral submucous fibrosis showed direct association with grade of hearing impairment and eustachian tube dysfunction. Higher clinical grades, both clinically and histologically showed similar findings thereby we concluded that if the disease is treated early, preventing patients from having higher grades of disease, involvement of ear can be avoided, and patients can be saved from hearing impairment.

Aims Odontogenic orbital cellulitis represents a complication of root infections of upper pre-molars and molars. The severity depends on the orbital structure involved. The treatment is based on antibiotic therapy associated or not to surgery. Through the presentation of three cases and a review of literature, we purpose as aim of our study to underline the necessity of a timely diagnosis and to provide the correct surgical approach in each different types and stages of orbital infections. Methods We present three patients that were affected by dental infection evolved in orbital cellulitis. In two cases the disease was solved with the extraction of infected tooth and a surgical endoscopic drainage of the abscess through antrostomy of maxillary sinus. In the third patient the disease had already induced a bulbar perforation and endophthalmitis, so an orbit evisceration was necessary. Results Review of literature showed that the standard treatment of orbital cellulitis is the transnasal approach associated or not by a transoral and/or transcutaneous procedure depending on the stage of the disease and on the causes. In our 3 cases these indications were followed without relapses of the disease. Conclusion An early diagnosis is mandatory in odontogenic orbital cellulitis specially to avoid serious complications. Surgical treatment can be simple and effective mostly in early-stage infection: it is based on extraction of infected tooth and on the drainage of abscess. Surgical approach consists in transnasal procedure flanked or not by transoral and transcutaneous procedures based on the stage of the infection considering involved structures.

Cancer in the head and neck region is among the most common cancer around the world, the incidence of which keep increasing in past years. Treatment of disease is usually done by the surgical excision which often leads to some degree of facial disfigurements which cause mutilation in patients. Mutilation imparts the feeling of stigma in patients, and patients usually tend to hide facial disfigurements using additional clothing. As a prevention strategy, awareness regarding the disease conveys to the mass population via media commercials. Media commercials which highlight the adverse outcomes of cancer are found to target the stigmatized perspective of disease. On the brighter side, more stigmatized is the patient image in the commercials, more motivation it will create in masses to avoid risk factors like tobacco, smoking and alcohol. But on the darker side, stigmatized commercials create a social environment in which people tend to maintain social distance to cancer patients, and patients have to bear social disapproval by society for their whole life. It reduces the self-esteem and quality of life of patients which affects their overall survival. In the present article, we review the status of stigma in head and neck cancer patients, tools that are available for assessment of stigma, and effects of the stigmatized media commercials on the patient's self-esteem. The present article represents the accurate picture of the problem and highlights the policies which could be employed to balance the paradox of stigmatized media commercials and a healthy social environment for cancer patients.

In this study, we hypothesized that social anxiety disorder would be more common in women with lower education levels and that this could have a negative effect on acoustic parameters. A total of eighty-eight (88) healthy female volunteers were enrolled into the study. These volunteers were divided into two groups, which were categorized as those with graduation from elementary school or below (Group A, n = 42) and those with graduation from high school or above (Group B, n = 46). Personal anxiety and avoidance for all participants were evaluated using The Liebowitz Social Anxiety Scale. All subjects also underwent acoustic and aerodynamic voice analysis for evaluation of their objective voice quality and function. Additionally, the GRBAS scale was used for perceptual analysis. Social anxiety scores were higher in group A than group B (p < 0.05). In aerodynamic sound analysis, maximal phonation time was lower in group A than group B (p < 0.05). In perceptual sound analysis, the mean values of the GRBAS parameters for group B were lower than group A (p < 0.05). Mean F0 of Group-B was higher than Group-A in acoustic analysis (p < 0.05). However, there was no statistical difference in jitter, shimmer, NHR and HNR between the groups (p > 0.05). In this study, social anxiety and education has been shown to have an effect on voice in women. As the level of education increases, social anxiety decreases, and both maximum phonation time and fundamental frequency increase.

For a chronically discharging ear open mastoidectomy is the mainstay of treatment, however it can cause high morbidity due a large cavity and complications like discharge, vertigo and difficulty with hearing aids. To avoid such problem, obliteration of mastoid cavity is done. The objective of our study was to compare the post-operative complains, the hearing results and outcomes of open and closed mastoid cavity. The present prospective study was conducted on 40 patients having attico-antral disease in middle ear cleft. Patients were randomly divided into two groups of 20 each. Out of 40 patients, in 20 patients (Group A) mastoid obliteration was done using conchal cartilage, whereas in other 20 patients (Group B) canal wall down mastoidectomy without mastoid obliteration was done i.e.an open cavity. The patients were followed up post-operatively at 6th week, 3rd month and 6th month. Study Design: comparative study. On Pure Tone Audiometry, 13 (65%) patients with closed mastoid cavity had Air-bone Gap < 30 dB, 7 (35%) were in the range 30-60 dB as compared to open mastoid cavity where 10 (20%), 8 (40%), 2(10%) patients had ABG < 30db, 30-60 dB, and > 60 dB respectively, showing better hearing results in obliterated cavities, healing was also better. In obliterated mastoid cavities, there were very few complications of pain, discharge, and giddiness compared to open cavities. Healing as shown by epithelisation was earlier and better in obliterated cavities. Hearing results were better in mastoid cavities with obliteration compared to open cavities. Patients with obliterated mastoid cavity need less cavity care and doctor dependence.

Phyllodes is a rare tumor found exclusively in females. It can be classified into benign, intermediate, or malignant variety based on the aggressive nature of the disease. With adequate preoperative clinical assessment combined with histopathology and radiological investigations the adequate treatment strategy can be formulated to avoid future recurrences. Complete androgen insensitivity syndrome (CAIS) is associated with a genotypic male, which can be confirmed by karyotyping, with phenotypic female characteristics. The present case is the first case of bilateral breast phyllodes tumor in a patient with CAIS. Preoperative assessment was suggestive of bilateral phyllodes tumor with bilateral gonads in the inguinal region which was confirmed to be testis postoperatively on histopathological analysis. A brief case report with review of literature is presented.

Low maxillary bone density associated with physiological bone remodeling and resorption accelerated by the presence or history of periodontal disease can prevent implant placement without either ridge and/or sinus augmentation in atrophic maxillary edentulous cases. As an alternative to avoid bone grafting and provide immediacy in restorative treatment care for the patient, remote anchorages to the basal bones of the maxilla of the patient are being used with zygomatic or pterygoid implants. The trans-sinus implant, when indicated can offer a reliable alternative to the zygomatic dental implant in that treatment of the severely edentulous maxilla. This approach is suggested in Bedrossian zones I and II atrophy and when an 'L' (or concave) anterior sinus wall anatomy is present. This approach will be discussed utilizing two case examples on how trans-sinus implants may be considered in treating the maxillary arch.

Hypereosinophilic syndrome (HES) is a rare condition characterized by hypereosinophilia in peripheral blood or tissue infiltrate and organ damage. HES has been associated with several diseases, including inflammatory bowel diseases (IBDs), especially ulcerative colitis (UC). In this report, we describe a case of a UC and primary sclerosing cholangitis patient who was diagnosed with HES and severe cardiovascular and neurological injury. During hospitalization, an extensive diagnostic workup was performed and secondary causes of hypereosinophilia were ruled out. The patient was treated with glucocorticoids and full anticoagulation with significant clinical improvement and a marked reduction in the eosinophil count. In the literature, hypereosinophilia in the IBD population has been related to the severity of the disease and worse prognosis. The high index of clinical suspicion and the accurate diagnosis of HES are essential to avoid delay in therapy and prevent complications.

In addition to attaining complete or near complete cytoreduction, the instillation of select heated chemotherapeutic agents into the abdominal cavity has offered a chance for cure or longer survival inpatients with peritoneal surface malignancies. While the heating of chemotherapeutic agents enhances cytotoxicity, the resulting systemic hyperthermia has been associated with an increased risk of severe hyperthermia and its associated complications. Factors that have been associated with an increased risk of severe hyperthermia include intraoperative blood transfusions and longer perfusion duration. However, the development of severe hyperthermia still remains largely unpredictable. Thus, at several institutions, cooling protocols are employed during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Cooling protocols for CRS-HIPEC are not standardized and may be associated with episodes of severe hyperthermia or alternatively hypothermia. In theory, excessive cooling could result in a decreased effectiveness of the intraperitoneal chemotherapeutic agents. This presumption has been supported by a recent study of 214 adults undergoing CRS-HIPEC, where failure to attain a temperature of 38° C at the end of chemo-perfusion was associated with worse survival. Although not statistically significant, failure to maintain a temperature of 38° C for at least 30 minutes was associated with worse survival. Although studies are limited in this regard, the importance of maintaining a steady state of temperature during the hyperthermic phase of intraperitoneal chemotherapy administration cannot be disregarded. The following article describes the processes and physiological mechanisms responsible for hyperthermia during CRS-HIPEC. The challenges associated with temperature management during CRS-HIPEC and methods to avoid severe hypothermia and hyperthermia are also described.

Targeting the endocannabinoid system may have a role in the treatment of post-traumatic stress disorder (PTSD). However, few studies have examined the effectiveness of cannabis on symptoms of PTSD, and more research is needed to ascertain cannabis' effectiveness. In this retrospective naturalistic study, we followed 14 relatively mature (32-68 years of age), treatment-resistant, chronic combat post-traumatic patients who remained severely symptomatic despite treatment with many lines of conventional treatment prior to receiving medicinal cannabis. Our findings show that total sleep score, subjective sleep quality, and sleep duration significantly improved (p < 0.01). Total PTSD symptom score and its subdomains (intrusiveness, avoidance, and alertness) showed improvement (p < 0.05). However, there was no improvement in the frequency of nightmares (p = 0.27). The mean follow-up time was 1.1 ± 0.8 years (range of 0.5 to 3 years).

During the COVID-19 pandemic, older people and patients with psychiatric disorders had an increased risk of being isolated. The French National Authority for Health has recommended a reinforced follow-up of these patients. Cross-sectional studies reported an increased risk of developing anxiety and depression during pandemic. The aim of our study was to identify factors associated with higher anxiety during the pandemic in older patients with psychiatric disorders.

Diffuse tenosynovial giant cell tumor (TGCT), also known as pigmented villonodular synovitis, is a benign, neoplastic disease of the synovium that can lead to joint destruction, osteoarthritis, and long-term morbidity1,2. Often, there is extra-articular involvement in the intercondylar notch and posterior soft tissues. A complete anterior and posterior synovectomy of the knee is indicated for treating diffuse TGCT when the anterior and posterior compartments of the knee joint are involved. Additionally, either an anterior or posterior synovectomy may be performed when the TGCT is limited to 1 compartment of the knee. Although an anterior synovectomy is relatively straightforward technically, a posterior synovectomy is challenging because of the presence of the neurovascular and muscular structures, which limit access, and because of the infrequency of the procedure.