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Titanium (Ti) and its alloys have been widely used as orthopedic implants, because of their favorable mechanical properties, corrosion resistance and biocompatibility. Despite their significant success in various clinical applications, the probability of failure, degradation and revision is undesirably high, especially for the patients with low bone density, insufficient quantity of bone or osteoporosis, which renders the studies on surface modification of Ti still active to further improve clinical results. It is discerned that surface physicochemical properties directly influence and even control the dynamic interaction that subsequently determines the success or rejection of orthopedic implants. Therefore, it is crucial to endow bulk materials with specific surface properties of high bioactivity that can be performed by surface modification to realize the osseointegration. This article first reviews surface characteristics of Ti materials and various conventional surface modification techniques involving mechanical, physical and chemical treatments based on the formation mechanism of the modified coatings. Such conventional methods are able to improve bioactivity of Ti implants, but the surfaces with static state cannot respond to the dynamic biological cascades from the living cells and tissues. Hence, beyond traditional static design, dynamic responsive avenues are then emerging. The dynamic stimuli sources for surface functionalization can originate from environmental triggers or physiological triggers. In short, this review surveys recent developments in the surface engineering of Ti materials, with a specific emphasis on advances in static to dynamic functionality, which provides perspectives for improving bioactivity and biocompatibility of Ti implants.

Extracellular vesicles (EVs) are nano-scale vesicles derived by cell secretion with unique advantages such as promoting cell proliferation, anti-inflammation, promoting blood vessels and regulating cell differentiation, which benefit their wide applications in regenerative medicine. However, the in vivo therapeutic effect of EVs still greatly restricted by several obstacles, including the off-targetability, rapid blood clearance, and undesired release. To address these issues, biomedical engineering techniques are vastly explored. This review summarizes different strategies to enhance EV functions from the perspective of drug loading, modification, and combination of biomaterials, and emphatically introduces the latest developments of functionalized EV-loaded biomaterials in different diseases, including cardio-vascular system diseases, osteochondral disorders, wound healing, nerve injuries. Challenges and future directions of EVs are also discussed.

As a new type of injectable biomaterials, functional microspheres have attracted increasing attention in tissue regeneration because they possess some advantageous properties compared to other biomaterials, including hydrogels. A variety of bio-inspired microspheres with unique structures and properties have been developed as cellular carriers and drug delivery vehicles in recent years. In this review, we provide a comprehensive summary of the progress of functional and biodegradable microspheres that have been used for tissue regeneration over the last two decades. First, we briefly introduce the biomaterials and general methods for microsphere fabrication. Next, we focus on the newly developed technologies for preparing functional microspheres, including macroporous microspheres, nanofibrous microspheres, hollow microspheres, core-shell structured microspheres, and surface-modified functional microspheres. After that, we discuss the application of functional microspheres for tissue regeneration, specifically for bone, cartilage, dental, neural, cardiac, and skin tissue regeneration. Last, we present our perspectives and future directions of functional microspheres as injectable carriers for the future advancement of tissue regeneration.

The goal of this review article, based on a systematic literature search, is to critically assess the state of knowledge and experimental methodologies used to delineate the conversion and metabolism of the 2 methionine (Met) sources DL-methionine (DL-Met) and DL-2-hydroxy-4-(methylthio) butanoic acid (HMTBa). The difference in the chemical structures of HMTBa and DL-Met indicates that these molecules are absorbed and metabolized differently in animals. This review explores the methodologies used to describe the 2-step enzymatic conversion of the 3 enantiomers (D-HMTBa, L-HMTBa and D-Met) to L-Met, as well as the site of conversion at the organ and tissue levels. Extensive work was published documenting the conversion of HMTBa and D-Met into L-Met and, consequently, the incorporation into protein using a variety of in vitro techniques, such as tissue homogenates, cell lines, primary cell lines, and everted gut sacs of individual tissues. These studies illustrated the role of the liver, kidney, and intestine in the conversion of Met precursors into L-Met. A combination of in vivo studies using stable isotopes and infusions provided evidence of the wide conversion of HMTBa to L-Met by all tissues and how some tissues are net users of HMTBa, whereas others are net secreters of L-Met derived from HMTBa. Conversion of D-Met to L-Met in organs other than the liver and kidney is poorly documented. The methodology cited in the literature to determine conversion efficiency ranged from measurements of urinary, fecal, and respiratory excretion to plasma concentration and tissue incorporation of isotopes after intraperitoneal and oral infusions. Differences observed between these methodologies reflect differences in the metabolism of Met sources rather than differences in conversion efficiency. The factors affecting conversion efficiency are explored in this paper and are mostly associated with extreme dietary conditions, such as noncommercial crystalline diets that are very deficient in total sulfur amino acids with respect to requirements. Implications in the diversion of the 2 Met sources toward transsulfuration over transmethylation pathways are discussed. The strengths and weaknesses of some methodologies used are discussed in this review. From this review, it can be concluded that due to the inherent differences in conversion and metabolism of the 2 Met sources, the experimental methodologies (e.g., selecting different organs at different time points or using diets severely deficient in Met and cysteine) can impact the conclusions of the study and may explain the apparent divergences of conclusion found in the literature. It is recommended when conducting studies or reviewing the literature to properly select the experimental models that allow for differences in how the 2 Met precursors are converted to L-Met and metabolized by the animal to enable a proper comparison of their bioefficacy.

This review compared the effects of eccentric versus concentric exercise training in healthy people and people with metabolic disease. A systematic search on Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, SPORTDiscus, Web of Science, SCOPUS and PubMed was conducted in February 2022. Randomised controlled trials conducted on sedentary healthy adults or those with an existing metabolic disease that compared eccentric versus concentric exercise training interventions of four weeks or longer that involved multiple joints and large muscle groups (e.g., walking, whole-body resistance training) were included in the review. The primary outcome was glucose handling, measured as HbA1c, HOMA, fasting glucose or insulin. Measures of cardiovascular health, muscle strength, and functional physical fitness were secondary outcomes. Nineteen trials involving 618 people were included. Results of meta-analyses showed that eccentric exercise had no benefit to glucose handling (HbA1c level; SMD - 0.99; 95% CI, -2.96 to 0.98; n = 74; P = 0.32) but resulted in significant increases in overall muscle strength (SMD 0.70; 95% CI 0.25 to 1.15; n = 224; P = 0.003) and decreases in blood pressure (Systolic Blood Pressure; MD -6.84; 95% CI, -9.84 to -3.84; n = 47, P = 0.00001, and Diastolic Blood Pressure; MD -6.39; 95% CI -9.62 to -3.15; n = 47, P = 0.0001). Eccentric exercise is effective for improving strength and some markers of cardiovascular health compared to traditional exercise modalities. Additional high-quality studies are necessary to validate these results. (PROSPERO registration: CRD42021232167).

As the human population increases globally, the food animal industry has not been spared from the monumental demand for edible animal products, particularly meat. This has necessitated the simultaneous expansion of the productivity of the animal sector to meet the ever-growing human needs. Although antibiotics have been used in food animal production with commendable positive impacts on their growth performance, their sole contributive factor to the increasing incidence of antimicrobial resistance has ushered the strict restrictions placed on their use in the animal sector. This has handed a setback to both animals and farmers; thus, the intense push for a more sustainable antibiotic alternative for use in animal production. The use of plants with concentrated phytogenic compounds has gained much interest due to their beneficial bioactivities, including antioxidant and selective antimicrobial. While the reported beneficial activities of phytogenic additives on animals vary due to their varying total polyphenol concentrations (TPC), red osier dogwood (ROD) plant materials boast of high TPC with excellent antioxidant prowess and growth improvement capacities compared to some plant extracts commonly used in research. However, its adoption in research and commercial scale is still low. Thus, the present review aims to provide concise information on the dietary potential of ROD plant materials in animal feeding.

Spindle cell lipoma (SCL) is a benign adipocytic tumor that primarily occurs in the subcutis of the posterior neck, upper back, and shoulder, particularly of middle-aged males. SCL and pleomorphic lipoma (PL) represent a morphological spectrum of one disease process. The lesion typically presents as a relatively small (

Alterations in significant genes located on chromosome 7 - including epidermal growth factor receptor (EGFR) and also v-Raf murine sarcoma viral oncogene homolog B (BRAF) as a mitogen-activated protein kinase (MAPK) - combined or not with numerical imbalances of the whole chromosome (aneuploidy-polysomy) are crucial genetic events involved in the development and progression of malignancies. Identification of EGFR/BRAF-dependent specific somatic mutations and other mechanisms of deregulation (i.e., amplification) is critical for applying targeted therapeutic approaches [tyrosine kinase inhibitors (TKIs] or monoclonal antibodies (mAbs). Thyroid carcinoma is a specific pathological entity characterized by a variety of histological sub-types. Follicular thyroid carcinoma (FTC), papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC) represent its main sub-types. In the current review, we explore the role of EGFR/BRAF alterations in thyroid carcinoma in conjunction with the corresponding anti-EGFR/BRAF TKI-based novel therapeutic strategies for patients with specific genetic signatures.

Background: Prostate cancer recurrence after definitive local therapy usually involves the bone and regional lymph nodes. Case Report: We present the case of a 72-year-old male patient with an isolated lung nodule, seven years after radical prostatectomy for prostate cancer, pT2bN0 and Gleason score 7(4+3), and prostatic-specific antigen (PSA) levels within normal limits. The nodule was considered as a primary lung cancer and the patient was subjected to lobectomy. The immunohistochemical staining showed that the tumor was PSA(+) and NKX3.1 (+), revealing that it was metastasis from prostatic cancer and that wedge resectomy was the proper procedure. Three years later the patient is disease-free, suggesting the importance of aggressive treatment of oligometastatic disease. Conclusion: Metastasis to the lung is present in more than 40% of men with metastatic prostate cancer; however, lung metastases without any bone or lymph node involvement are extremely rare and only a handful of cases are reported in the literature. Surgical excision of the metastatic lung site is the most common therapeutic approach associated with a good prognosis.

Background/Aim: Primary testicular lymphoma (PTL) is an exceedingly rare and aggressive form of non-Hodgkin’s lymphoma; the most common subtype is diffuse large B-cell (DLBCL). Standard treatment includes orchiectomy, chemotherapy, central nervous system (CNS) prophylaxis, and prophylactic radiation to the contralateral testis. PTL can reoccur years after complete remission. Treatment to immune sanctuary sites, CNS and contralateral testis, is crucial in preventing relapse. There are limited data characterizing this entity and this study aimed to add to existing literature. Patients and Methods: This descriptive retrospective study characterized twelve patients with PTL from years 2010-2021 at Allegheny Health Network. Their demographic data, prognostic factors, treatment regimens, and relapse sites (if any) were tabulated. The mean progression-free survival (PFS) was calculated to describe our experience in treating PTL. Results: Twelve patients were diagnosed with PTL; 10/12 (83.33%) patients were diagnosed with ABC PTL-DLBCL. Median age of diagnosis was 67 years. Eight of the 12 (66.66%) were African American, 4/12 (33.33%) were Caucasian. At the time of diagnosis, 8/12 (66.66%) patients presented with an elevated lactate dehydrogenase (LDH) and 8/12 (66.66%) presented with a left testicular mass. Most were treated with R-CHOP (9/12), intrathecal methotrexate (IT-MTX) (10/12), and radiation to the contralateral testis (9/12). Three of the twelve (25%) patients relapsed. Median time to relapse was 8 months. Mean PFS was 50.417 months. Conclusion: We discuss our experience in treating PTL with RCHOP, IT-MTX, and irradiation to the contralateral testis and add to the limited pre-existing data that exist.

Objective: Salivary pepsin has emerged as a biomarker for Laryngopharyngeal Reflux (LPR), which, however, has been questioned for its efficacy due to a lack of supporting medical data. Therefore, this study analyzed the diagnostic value of salivary pepsin for LPR and assessed a better cutoff value. Methods: Studies were searched in PubMed, Embase, and Cochrane Library from their receptions to October 1, 2021. Then, RevMan 5.3 and Stata 14.0 were utilized to summarize the diagnostic indexes for further meta-analysis. Data were separately extracted by two reviewers according to the trial data extraction form of the Cochrane Handbook. The risk of bias in Randomized Control Trials (RCTs) was evaluated with the Cochrane Risk of Bias Tool. Results: A total of 16 studies matched the criteria and were subjected to meta-analysis. The results revealed a pooled sensitivity of 61% (95% CI 50%–71%), a pooled specificity of 67% (95% CI 48%–81%), a positive likelihood ratio of 2 (95% CI 1.2–2.8), a negative likelihood ratio of 0.58 (95% CI 0.47–0.72), and the area under the receiver operating characteristic curve of 0.67 (95% CI 0.63–0.71). Subgroup analyses indicated that the cutoff value of pepsin at 50 ng/mL had a higher degree of diagnostic accuracy than that of pepsin at 16 ng/mL in cohort studies. Conclusion: The review demonstrated low diagnostic performance of salivary pepsin for LPR and that the cutoff value of 50 ng/mL pepsin had superior diagnostic accuracy. Nevertheless, the diagnostic value may vary dependent on the utilized diagnostic criteria. Therefore, additional research is needed on the improved way of identifying salivary pepsin in the diagnosis of LPR, and also longer-term and more rigorous RCTs are warranted to further assess the effectiveness of salivary pepsin.

OBJECTIVE: The objective of this article is to review the most current literature on vaccines, focusing on their safety, immunogenicity, and efficacy in preterm newborns, aiming to improve vaccine coverage in this population. DATA SOURCE: Most recent scientific publications addressing the immunization of preterm newborns. DATA SYNTHESIS: Despite its immunological immaturity, vaccination is well tolerated by preterm infants, and protective immune responses are observed, but some studies have shown that preterm infants undergo unjustified delays in their vaccination schedule. CONCLUSIONS: Despite being widely recommended, the routine immunization of preterm infants is often delayed, putting this vulnerable population at risk for several diseases, many of which are preventable by immunization. Every effort should be made to develop universal guidelines that define the immunization of preterm infants.

Skeletal muscle is one of the leading frameworks of the musculo-skeletal system, which works in synergy with the bones. Long skeletal muscles provide stability and mobility to the human body and are primarily composed of proteins. Conversely, improper functioning of various skeletal muscles leads to diseases and disorders, namely, age-related muscle disorder called sarcopenia, a group of genetic muscle disorders such as muscular dystrophies, and severe muscle wasting in cancer known as cachexia. However, skeletal muscle has an excellent ability to undergo hypertrophy and enhanced functioning during sustained exercise over time. Indeed, these processes of skeletal muscle regeneration/hypertrophy, as well as degeneration and atrophy, involve an interplay of various signaling pathways. Myostatin is one such chemokine/myokine with a significant contribution to muscle regeneration or atrophy in multiple conditions. In this review, we try to put together the role and regulation of myostatin as a function of muscle regeneration extrapolated to multiple aspects of its molecular functions.

OBJECTIVE: To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and antimicrobial resistance in Brazil since its introduction in 2010. DATA SOURCE: A narrative review of English, Spanish, and Portuguese articles published in online databases and in Brazilian epidemiological surveillance databases was performed. The following keywords were used: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccine, PCV10, antimicrobial resistance, and meningitis. SUMMARY OF THE FINDINGS: Declines in hospitalization rates of all-cause pneumonia occurred in the target age groups and some age groups not targeted by vaccination early after the use of PCV10. Large descriptive studies of laboratory-confirmed pneumococcal meningitis and hospital-based historical series of hospitalized children with IPD have evidenced a significant impact on disease burden, in-hospital fatality rates, and admission to the intensive care unit before and after the inclusion of the vaccine. Impact data on otitis media is limited and inconsistent; the main benefit remains the prevention of complicated diseases. During the late post-vaccine years, a significant and progressive increase in high-level penicillin non-susceptibility pneumococci has been described. Since 2014 serotype 19A has been the leading serotype in all ages and was responsible for 28.2%–44.6% of all IPD in children under 5 yrs. CONCLUSIONS: PCV10 has performed a significant impact on IPD in Brazil since 2010, however, progress has been continuously hampered by replacement. Broader spectrum PCVs could provide expanded direct and indirect protection against ST19A and other additional serotypes of increasing importance if administered to children in the Brazilian National Immunization Program.

Patients with disseminated colorectal cancer have a dismal prognosis with a 5-year survival rate of only 13%. In order to identify new treatment modalities and new targets, we searched the literature for up-regulated circular RNAs in colorectal cancer which induce tumor growth in corresponding preclinical in vivo models. We identified nine circular RNAs that mediate resistance against chemotherapeutic agents, seven that up-regulate transmembrane receptors, five that induce secreted factors, nine that activate signaling components, five which up-regulate enzymes, six which activate actin-related proteins, six which induce transcription factors and two which up-regulate the MUSASHI family of RNA binding proteins. All of the circular RNAs discussed in this paper induce the corresponding targets by sponging microRNAs (miRs) and can be inhibited by RNAi or shRNA in vitro and in xenograft models. We have focused on circular RNAs with demonstrated activity in preclinical in vivo models because the latter is an important milestone in drug development. All circular RNAs with in vitro activity only data are not referenced in this review. The translational impact of inhibition of these circular RNAs and of the identified targets for treatment of colorectal cancer (CRC) are discussed.

OBJECTIVES: Since the beginning of its use for the prevention of tuberculosis (TB) in 1921, other uses of BCG (Bacillus Calmette-Guérin) have been proposed, particularly in the treatment of malignant solid tumors, multiple sclerosis, and other autoimmune diseases. Its beneficial impact on other infections, by nontuberculous mycobacteria, and by viruses, has been more often studied in recent years, especially after the introduction of the concept of trained immunity. The present study's objective was to review the possible indications of BCG and the immunological rationale for these indications. DATA SOURCE: Non-systematic review carried out in the PubMed, SciELO and Google Scholar databases, using the following search terms: “BCG” and “history”, “efficacy”, “use”, “cancer”, “trained immunity”, “other infections”, “autoimmune diseases”. DATA SYNTHESIS: There is epidemiological evidence that BCG can reduce overall child morbidity/mortality beyond what would be expected from TB control. BCG is able to promote cross-immunity with nontuberculous mycobacteria and other bacteria. BCG promotes in vitro changes that increase innate immune response to other infections, mainly viral ones, through mechanisms known as trained immunity. Effects on cancer, except bladder cancer, and on autoimmune and allergic diseases are debatable. CONCLUSIONS: Despite evidence obtained from in vitro studies, and some epidemiological and clinical evidence, more robust evidence of in vivo efficacy is still needed to justify the use of BCG in clinical practice, in addition to what is recommended by the National Immunization Program for TB prevention and bladder cancer treatment.

OBJECTIVES: Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy. DATA SOURCE: A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022. DATA SYNTHESIS: Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population. CONCLUSIONS: The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.

Cardiovascular diseases, a global health issue, claim the lives of many every year. Lifestyle changes and genetic predisposition are the key drivers for the development of CVDs. In many of the patients, the disease is detected at the end stage making heart transplantation the only treatment option. Hence every attempt should be made to identify the risk at an early stage and initiate preventive measures to improve the quality of their life. Biomarkers are one of the critical factors that aid in the early diagnosis of CVDs. More specific and highly sensitive biomarkers have been discovered lately and have been employed for prognosis and diagnosis of CVDs. The present review briefs about the various categories of cardiovascular biomarkers with emphasis on novel biomarkers and discusses the biomarkers employed for different purposes in CVDs. The biomarkers have also helped in identifying COVID-19 patients with increased risk for developing cardiovascular complications. Being non-invasive makes biomarkers advantageous over other methods for evaluating the pathophysiological status of CVDs.

OBJECTIVE: Through a literature review, make recommendations regarding immunizations in people living with Inborn Error of Metabolism (IEM) in Brazil, assess the possible impact on metabolic decompensations after immunization, and if this specific population may have an impaired immune response to vaccines. SOURCE OF DATA: The MeSH Terms vaccination OR vaccine OR immunization associated with the term inborn error of metabolism AND recommendation were used in combination with search databases. Only articles published after 1990, in the languages English, Spanish, French or Portuguese, human-related were included. SYNTHESIS OF DATA: A total of 44 articles were included to make the following recommendations. Individuals with IEMs need to be up to date with their immunizations. Regarding which vaccines should be offered, children and adults should follow the routine immunization schedules locally available, including the COVID-19 vaccines. The only exception is the rotavirus vaccine for hereditary fructose intolerance. The benefit of immunization outweighs the very low risk of metabolic decompensation. Since not all patients will have an adequate immune response, measuring antibody conversion and titers is recommended CONCLUSIONS: All patients should receive age-appropriate immunizations in their respective schedules without delays. The only situation when vaccination may be contraindicated is with oral rotavirus vaccine in hereditary fructose intolerance. Monitoring the levels of antibodies should be done to detect any immune dysfunction or the necessity for boosters. A personalized immunization schedule is ideal for patients with IEMs. The reference organizations could improve their recommendations to address all IEMs, not only some of them.

BACKGROUND AND OBJECTIVES: In spite of bone’s healing capacity, critical-size bone defect regeneration and peri-implant osseointegration are challenging. Tissue engineering provides better outcomes, but requires expensive adjuncts like stem cells, growth factors and bone morphogenic proteins. Vitamin D (Vit.D) regulates calcium and phosphorus metabolism, and helps maintain bone health. Vit.D supplements in deficient patients, accentuates bone healing and regeneration. Therefore the aim of this systematic review was to evaluate the role of adjunctive Vit.D on bone defect regeneration. METHODS: Comprehensive database search of indexed literature, published between January 1990 and June 2022, was carried out. English language articles fulfilling inclusion criteria (clinical/in vivo studies evaluating bone regeneration including osseointegration and in vitro studies assessing osteogenic differentiation, with adjunct Vit.D) were identified and screened. RESULTS: Database search identified 384 titles. After sequential title, abstract and full-text screening, 23 studies (in vitro – 9/in vivo – 14) were selected for review. Vit.D as an adjunct with stem cells and osteoblasts resulted in enhanced osteogenic differentiation and upregulation of genes coding for bone matrix proteins and alkaline phosphatase. When used in vivo, Vit.D resulted in early and increased new bone formation and mineralization within osseous defects, and better bone implant contact and osseointegration, around implants. Adjunct Vit.D in animals with induced systemic illnesses resulted in bone defect regeneration and osseointegration comparable to healthy animals. While systemic and local administration of Vit.D resulted in enhanced bone defect healing, outcomes were superior with systemic route. CONCLUSIONS: Based on this review, adjunct Vit.D enhances bone defect regeneration and osseointegration. In vitro application of Vit.D to stem cells and osteoblasts enhances osteogenic differentiation. Vit.D is a potentially non-invasive and inexpensive adjunct for clinical bone regeneration and osseointegration. Long term clinical trials are recommended to establish protocols relating to type, dosage, frequency, duration and route of administration.

Objective: Weight loss is one of the most often prescribed treatments to reduce the level of sleep apnea severity; however, objective assessment of airway alterations after loss of weight has only been studied in the last decades. This study aimed at evaluating alterations after weight loss reported in the literature. Methods: A literature review was performed in the medical databases: PubMed, Web of Science, Scopus and Embase. A total of 681 articles were found in the databases and after evaluation only 10 studies were selected for data extraction. Results: Most studies observed an increase of the area in the retropalatal region; some indicating that this increase occurred mostly in the lateral pharyngeal region. Studies with volumetric reconstruction showed a significant reduction in parapharyngeal fat deposits, lateral wall and tongue fat, and volumetric reduction in all soft tissues of the pharynx, pterygoid and genioglossus muscles. Studies evaluating craniofacial bone structures showed a reduction in the airway height by bringing the hyoid closer to the posterior nasal spine and a reduction in the distance from the hyoid to the chin. Conclusion: There is a limited number of studies with a good level of scientific evidence evaluating changes in the upper airways after weight loss and how these changes impact obstructive sleep apnea. The studies included in this review indicate that weight loss increases the airways space by reducing the volume of the parapharyngeal structures, particularly at the retropalatal site, where there is an apparent gain in the lateral area of the airway and hyoid relocation.

OBJECTIVE: To present an updated review of recommendations for the vaccination of children with immune-mediated diseases, with an emphasis on rheumatic and inflammatory diseases. SOURCE OF DATA: Studies published in the PubMed and Scielo databases between 2002 and 2022, Guidelines of Brazilian Scientific Societies, Manuals and Technical Notes of the Ministry of Health of Brazil, on current immunization schedules for special populations. DATA SYNTHESIS: Immunosuppressive drugs and biological agents reduce the immunogenicity of vaccines and favor susceptibility to infections. The safety and efficacy of immunogens are important points for vaccination in children with immune-mediated diseases. The safety threshold of a vaccine applied to immunocompromised individuals can be reduced when compared to healthy individuals. Very often, the recommendations for the immunization of children with immune-mediated diseases follow the recommendations for immunocompromised patients. Vaccination against COVID-19, on the other hand, should ideally occur when the disease is stabilized and in the absence of a low degree of immunosuppression. The patients should be informed about the possibility that the immunization may fail during treatment with immunosuppressants. Specific vaccination schedules should be considered to ensure better protection. CONCLUSIONS: Recent studies have allowed updating the recommendations on the safety and immunogenicity of vaccination in children with immune-mediated diseases, especially for live attenuated vaccines. There is a scarcity of data on the safety and efficacy of COVID-19 vaccines in patients, particularly pediatric patients, with rheumatic diseases. The completion of ongoing studies is expected to help guide recommendations on COVID-19 vaccines in this group of patients.

In recent years, electromagnetic field (EMF) therapy has gathered much attention for its protective effects on cardiovascular functions. From reviewing the literature, it is evident that exposure to specific EMF spectrums, such as static- and extremely low frequency (ELF)- EMFs, by EMF-generating devices can be considered as a safe method for therapeutic means in various cardiovascular diseases, including heart failure, cardiac arrhythmias, and hypertension. This review article will describe registered patents and non-invasive clinically effective devices that generate EMF to target various cardiovascular diseases based on their mechanism of therapeutic effects.

While previous research has indicated that alcohol use is associated with difficulties in emotion processing and socioemotional functioning, less is known about the effects of cannabis on these functions. The purpose of this review article is to provide the current state of knowledge on the effects of cannabis on emotion processing with regard to behavioral, physiological, and neural responses. This narrative review synthesizes previous research investigating the effects of cannabis on emotion processing across studies that have utilized a number of experimental approaches to determine both the acute and chronic effects of cannabis on emotion processing. Limitations of current research and steps for future directions are discussed. Existing research has shown that cannabis use is associated with difficulties in emotion processing, such as impairments in correctly identifying emotions and problems with emotion differentiation. Electroencephalography (EEG) studies have produced mixed findings, but have considered a number of variables, such as participant sex, and comorbid depression. In addition, while there are mixed findings for the effects of cannabis on amygdalar brain activity across functional magnetic resonance imaging studies, several studies indicate that cannabis use is linked with decreased brain response in the frontal lobe while viewing emotional stimuli. To our knowledge, this is one of the first critical review articles focused on an emerging research area of cannabis and emotion processing. Synthesizing the existing findings in this developing research field is important for future prevention and intervention studies focused on promoting healthy socioemotional functioning in cannabis users. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background/Aim: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, resulting in pain, numbness, instability, and thus affecting quality of life (QoL), occasionally leading to discontinuation of chemotherapy. Pharmacological treatments are not sufficient. Non-pharmacological interventions (NPIs) have also been tried. This study aimed to systematically review the efficacy of NPIs on pain and QoL in patients suffering from CIPN. Materials and Methods: The databases searched were Pubmed, Cohrane, and Scopus for randomized controlled trials (RCTs) published in the last 5 years (2017- 2022). Studies were considered eligible, if they assessed adult patients suffering from CIPN because of any chemotherapeutic drug for any type and any stage of cancer and if study protocols included non-pharmacological intervention with a structured protocol. Results: A total of 1,496 records were identified. Finally, 10 RCTs including 495 patients (253 in the intervention group and 242 in the control group) were included for meta-analysis. Intervention protocols included acupuncture (n=6), exercise (n=3), and yoga (n=1). NPIs significantly reduced neuropathic pain. However, the effect on QoL was not significant. Conclusion: NPIs are beneficial in the treatment of pain in patients with CIPN but their impact on QoL is not statistically supported. Larger sample sizes, more homogenous in outcome measures and interventions are needed to further explore NPIs’ efficacy on CIPN symptoms.

Melanoma is one of the most dangerous types of cutaneous neoplasms, which are pigment-producing cells of neuroectodermal origin found all over the body. A great deal of research is focused on the mechanisms of melanoma to promote better diagnostic and treatment options for melanoma in its advanced stages. The progression of melanoma involves alteration in different levels of gene expression. With the successful implementation of next-generation sequencing technology, an increasing number of long noncoding RNAs (lncRNAs) sequences have been discovered, and a significant number of them have phenotypic effects in both in vitro and in vivo studies, implying that they play an important role in the occurrence and progression of human cancers, particularly melanoma. A number of evidence indicated that lncRNAs are important regulators in tumor cell proliferation, invasion, apoptosis, immune escape, energy metabolism, drug resistance, epigenetic regulation. To better understand the role of lncRNAs in melanoma tumorigenesis, we categorize melanoma-associated lncRNAs according to their cellular functions and associations with gene expression and signaling pathways in this review. Based on the mechanisms of lncRNA, we discuss the possibility of lncRNA-target treatments, and the application of liquid biopsies to detect lncRNAs in melanoma diagnosis and prognosis.

Cancer has received extensive recognition for its high mortality rate, with metastatic cancer being the top cause of cancer-related deaths. Metastatic cancer involves the spread of the primary tumor to other body organs. As much as the early detection of cancer is essential, the timely detection of metastasis, the identification of biomarkers, and treatment choice are valuable for improving the quality of life for metastatic cancer patients. This study reviews the existing studies on classical machine learning (ML) and deep learning (DL) in metastatic cancer research. Since the majority of metastatic cancer research data are collected in the formats of PET/CT and MRI image data, deep learning techniques are heavily involved. However, its black-box nature and expensive computational cost are notable concerns. Furthermore, existing models could be overestimated for their generality due to the non-diverse population in clinical trial datasets. Therefore, research gaps are itemized; follow-up studies should be carried out on metastatic cancer using machine learning and deep learning tools with data in a symmetric manner.

The last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic reprogramming. One of the most important cancer hallmarks, including aerobic glycolysis (the Warburg effect), the central carbon pathway, and multiple-branch metabolic pathway remodeling, enables tumor growth, progression, and metastasis. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key rate-limiting enzyme in gluconeogenesis, catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. PCK1 expression in gluconeogenic tissues is tightly regulated during fasting. In tumor cells, PCK1 is regulated in a cell-autonomous manner rather than by hormones or nutrients in the extracellular environment. Interestingly, PCK1 has an anti-oncogenic role in gluconeogenic organs (the liver and kidneys), but a tumor-promoting role in cancers arising from non-gluconeogenic organs. Recent studies have revealed that PCK1 has metabolic and non-metabolic roles in multiple signaling networks linking metabolic and oncogenic pathways. Aberrant PCK1 expression results in the activation of oncogenic pathways, accompanied by metabolic reprogramming, to maintain tumorigenesis. In this review, we summarize the mechanisms underlying PCK1 expression and regulation, and clarify the crosstalk between aberrant PCK1 expression, metabolic rewiring, and signaling pathway activation. In addition, we highlight the clinical relevance of PCK1 and its value as a putative cancer therapeutic target.

Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.

Blockchain is a technology for securely storing data in a manner that makes system changes or hacks impossible or difficult. Numerous organizations have adopted this technology, which utilizes a peer-to-peer distributed network. using a decentralized peer-to-peer network to operate. A blockchain is a collection of linked computer systems that operate as a distributed ledger of Cchain is made up of numerous transactions. This paper aims to explain blockchain technology, including its uses and difficulties.

Chronic inflammation caused by persistent infections and metabolic disorders is thought to contribute to the increased cancer risk and the accelerated cancer progression. Oppositely, acute inflammation induced by bacteria-based vaccines or that is occurring after cancer selectively inhibits cancer progression and metastasis. However, the interaction between inflammation and cancer may be more complex than the current explanations for the relationship between chronic and acute inflammation and cancer. In this review, we described the impact of inflammation on cancer on the basis of three perspectives, including inflammation with different durations (chronic and acute inflammation), different scopes (systemic and local inflammation) and different occurrence sequences (inflammation occurring after and before cancer). In addition, we also introduced bacteria/virus-based cancer immunotherapies. We perceive that inflammation may be a double-edged sword with cancer-promoting and cancer-suppressing functions in certain cases. We expect to further improve the understanding of the relationship between inflammation and cancer and provide a theoretical basis for further research on their complex interaction.

Hormone binding proteins (HBPs) belong to the group of soluble carrier proteins. These proteins selectively and non-covalently interact with hormones and promote growth hormone signaling in human and other animals. The HBPs are useful in many medical and commercial fields. Thus, the identification of HBPs is very important because it can help to discover more details about hormone binding proteins. Meanwhile, the experimental methods are time-consuming and expensive for hormone binding proteins recognition. Computational prediction methods have played significant roles in the correct recognition of hormone binding proteins with the use of sequence information and ML algorithms. In this review, we compared and assessed the implementation of ML-based tools in recognition of HBPs in a unique way. We hope that this study will give enough awareness and knowledge for research on HBPs.

Thermogenesis is a physiological activity of releasing heat that originates from intracellular biochemical reactions. Recent experimental studies discovered that externally applied heat changes intracellular signaling locally, resulting in global changes in cell morphology and signaling. Therefore, we hypothesize an inevitable contribution of thermogenesis in modulating biological system functions throughout the spatial scales from molecules to individual organisms. One key issue examining the hypothesis, namely, the "trans-scale thermal signaling," resides at the molecular scale on the amount of heat released via individual reactions and by which mechanism the heat is employed for cellular function operations. This review introduces atomistic simulation tool kits for studying the mechanisms of thermal signaling processes at the molecular scale that even state-of-the-art experimental methodologies of today are hardly accessible. We consider biological processes and biomolecules as potential heat sources in cells, such as ATP/GTP hydrolysis and multiple biopolymer complex formation and disassembly. Microscopic heat release could be related to mesoscopic processes via thermal conductivity and thermal conductance. Additionally, theoretical simulations to estimate these thermal properties in biological membranes and proteins are introduced. Finally, we envisage the future direction of this research field., 50 pages, 7 figures, 1 table, submitted to

Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%), craniosynostosis is presented as sporadic anomaly (non-syndromic craniosynostosis), while in other cases (15%) as part of syndromes (syndromic craniosynostosis). Patients with syndromic disorder usually have more severe symptoms compared to those with single suture synostosis. Most common syndromes of craniosynostosis include Pfeiffer, Apert, Crouzon, Jackson-Weiss, Muenke and Boston type MSX2-related syndrome. The main gene mutations in craniosynostosis involve FGFR1, FGFR2, FGFR3, TWIST1 and MSX2, which encode key factors influencing cranial bone morphogenesis. The main therapeutic approaches are surgical as discussed in this review, and the type of therapy depends on the graveness of the incident.

In order to identify new targets and treatment modalities for breast cancer, we searched the literature for circular RNAs (circRNAs) with efficacy in preclinical breast cancer-related in vivo models. From our search, we identified 26 up-regulated and six down-regulated circRNAs which mediate efficacy in breast cancer-related preclinical in vivo models. We discuss reconstitution and inhibition of the identified circRNAs, as well as druggability and validation of the targets identified in the context of chemoresistance, inhibition of proliferation and metastasis. Pathways driven by suppressors of cytokines and high-mobility group proteins, nuclear factor ĸB and Hippo signaling emerged as important drivers of tumor growth and metastasis. The role of trefoil factor-1 with respect to metastasis of estrogen receptor-positive breast cancer also merits further investigation. In addition, mucin 19 has emerged as an unexplored target for treatment of breast cancer.

SPINOPHILIN (SPN, PPP1R9B or NEURABIN-2) is a multifunctional protein that regulates protein–protein interactions in different cell signaling pathways. SPN is also one of the regulatory subunits of protein phosphatase 1 (PP1), implicated in the dephosphorylation of retinoblastoma protein (pRB) during cell cycle. The SPN gene has been described as a tumor suppressor in different human tumor contexts, in which low levels of SPN are correlated with a higher grade and worse prognosis. In addition, mutations of the SPN protein have been reported in human tumors. Recently, an oncogenic mutation of SPN, A566V, was described, which affects both the SPN–PP1 interaction and the phosphatase activity of the holoenzyme, and promotes p53-dependent tumorigenesis by increasing the cancer stem cell (CSC) pool in breast tumors. Thus, the loss or mutation of SPN could be late events that promotes tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor.

Invasive pancreatic ductal carcinoma is a representative refractory malignant tumor, and even with the development of early diagnosis and treatment techniques, the treatment outcome has been remarkably poor. Surgical resection is the curative treatment for resectable pancreatic cancer and borderline resectable pancreatic cancer. However, the survival rate in patients with pancreatic cancer treated by resection alone is low because of the high postoperative recurrence rate. In this review article, we report recent studies on perioperative treatment for pancreatic cancer. Perioperative therapy is the addition of chemotherapy or radiation therapy before or after surgery to improve resectability and curative effects. Because it is difficult to cure redsecttable pancreatic cancer by surgery alone, multidisciplinary treatment combined with perioperative adjuvant chemotherapy is the current standard of care. Although perioperative chemotherapy and chemoradiotherapy have been investigated for borderline resectable pancreatic cancer, the effectiveness of preoperative treatment has not been sufficiently proven. Potentially curative pancreatic cancer is treated by surgery plus perioperative therapy; treatment cannot be either alone. We regard the successful completion of surgery and perioperative care as the key to improving treatment outcomes. Therefore, ongoing randomized controlled trials for the treatment of BR-pancreatic cancer are expected to induce further improvements survival outcomes of patients with BR-pancreatic cancer.

One of the major hallmarks of many cancer cells is dedifferentiated cells (immature cells) with little or no resemblance to normal cells. Besides the poor differentiation, malignant cells also have important features such as aggressiveness and resistance to different therapeutics. Differentiation potentiators hold great promise for cancer treatment. Dimethyl sulfoxide (DMSO) is a well-characterized pharmaceutical solvent. It is used as a component of numerous cancer therapeutic approaches, including cancer treatment and several approved cancer immune therapeutics such as Car-T cell therapy and the FDA-approved drug Mekinist (trametinib DMSO) for melanoma treatment. It is also biologically recognized as a pharmaceutical solvent and cryoprotectant. In the current literature, there are no mentions of DMSO’s possible ability to potentiate therapeutic activity as a component of these cancer treatments. This review aimed to summarize scientific evidence and substantiate the concept that DMSO can contribute positively to the overall efficacy of cancer treatment as an adjuvant that is safe, inexpensive, and an effective differentiation-inducing therapeutic agent.

Obesity is a public-health challenge resulting from an imbalance between energy expenditure and calorie intake. This health problem exacerbates a variety of metabolic complications worldwide. Adipose tissue is an essential regulator of energy homeostasis, and the functions within it are regulated by purinergic receptors. A(1)R, P2X7R, and P2YR mainly mediate energy homeostasis primarily through regulating energy storage and adipokines secretion in white adipose tissue (WAT). P2X5R is a novel-specific cell surface marker in brown/beige adipocytes. A(2)R is a promising therapeutic target for stimulating energy expenditure in brown adipose tissue (BAT) and also mediating WAT browning. Based on these features, purinergic receptors may be an appropriate target in treating obesity. In this review, the role of purinergic receptors in different types of adipose tissue is summarized. An improved understanding of purinergic receptor functions in adipose tissue may lead to more effective treatment interventions for obesity and its related metabolic disorders.

Background: Cancer cases diagnosed each year are increasing, mainly because the population is ageing and, in part, due to early detection. This implies that there are more and more persons that receive medical anticancer therapies and that are interested in maintaining their quality of life. Many oncological treatments, including chemotherapy, immunotherapy, surgery, and radiotherapy, and combined therapy are associated with cutaneous toxicity and long-term side effects to different tissues and organs. This is particularly relevant when new therapies are used since these may cause new and unexpected side effects that may be short-lived but, in some cases, may become chronic or permanent. Patients often seek advice with their oncologists on what can be done and what cannot be done. Notably, many of the cutaneous side effects can be prevented or reduced by adequate interventions. Summary: The aim of this review is to highlight how oncological patients may benefit from a closer collaboration between specialists in different branches. We will focus on women with breast cancer since we think that they may derive a special benefit from this collaboration, but we will analyse other cancers in future papers. Key Messages: The working group was created to help the medical doctor in the prevention and management of all the adverse effects of the oncological treatments, supporting patients in this phase of their life, including nutritional assessment and dietary support.

Accumulating evidence underscores the large role played by the environment in the health of communities and individuals. We review the currently known contribution of environmental exposures and pollutants on kidney disease and its associated morbidity. We review air pollutants, such as particulate matter; water pollutants, such as trace elements, per- and polyfluoroalkyl substances, and pesticides; and extreme weather events and natural disasters. We also discuss gaps in the evidence that presently relies heavily on observational studies and animal models, and propose using recently developed analytic methods to help bridge the gaps. With the expected increase in the intensity and frequency of many environmental exposures in the decades to come, an improved understanding of their potential effect on kidney disease is crucial to mitigate potential morbidity and mortality.

A hyponatremic patient with the syndrome of inappropriate antidiuresis (SIAD) gets normal saline (NS), and the plasma sodium decreases, paradoxically. To explain, desalination is often invoked: if urine is more concentrated than NS, the fluid's salts are excreted while some water is reabsorbed, exacerbating hyponatremia. But comparing concentrations can be deceiving. They should be converted to quantities because mass balance is key to unlocking the paradox. The [sodium] equation can legitimately be used to track all of the sodium, potassium, and water entering and leaving the body. Each input or output "module" can be counterbalanced by a chosen iv fluid so that the plasma sodium stays stable. This equipoise is expressed in terms of the iv fluid's infusion rate, an easy calculation called the ratio profile. Knowing the infusion rate that maintains steady state, we can prescribe the iv fluid at a faster rate in order to raise the plasma sodium. Rates less than the ratio profile may risk a paradox, which essentially is caused by an iv fluid underdosing. Selecting an iv fluid that is more concentrated than urine is not enough to prevent paradoxes; even 3% saline can be underdosed. Drinking water adds to the ratio profile and is underestimated in its ability to provoke a paradox. In conclusion, the quantitative approach demystifies the paradoxical worsening of hyponatremia in SIAD and offers a prescriptive guide to keep the paradox from happening. The ratio profile method is objective and quickly deployable on rounds, where it may change patient management for the better.

Following prolonged neglect during the formative decades of behavioural neurology, the temporopolar region has become a site of vibrant research on the neurobiology of cognition and conduct. This turnaround can be attributed to increasing recognition of neurodegenerative diseases that target temporopolar regions for peak destruction. The resultant syndromes include behavioural dementia, associative agnosia, semantic forms of primary progressive aphasia and semantic dementia. Clinicopathological correlations show that object naming and word comprehension are critically dependent on the language-dominant (usually left) temporopolar region, whereas behavioural control and non-verbal object recognition display a more bilateral representation with a rightward bias. Neuroanatomical experiments in macaques and neuroimaging in humans show that the temporoparietal region sits at the confluence of auditory, visual and limbic streams of processing at the downstream (deep) pole of the ‘what’ pathway. The functional neuroanatomy of this region revolves around three axes, an anterograde horizontal axis from unimodal to heteromodal and paralimbic cortex; a radial axis where visual (ventral), auditory (dorsal) and paralimbic (medial) territories encircle temporopolar cortex and display hemispheric asymmetry; and a vertical depth-of-processing axis for the associative elaboration of words, objects and interoceptive states. One function of this neural matrix is to support the transformation of object and word representations from unimodal percepts to multimodal concepts. The underlying process is likely to start at canonical gateways that successively lead to generic (superordinate), specific (basic) and unique levels of recognition. A first sign of left temporopolar dysfunction takes the form of taxonomic blurring where boundaries among categories are preserved but not boundaries among exemplars of a category. Semantic paraphasias and coordinate errors in word–picture verification tests are consequences of this phenomenon. Eventually, boundaries among categories are also blurred and comprehension impairments become more profound. The medial temporopolar region belongs to the amygdalocentric component of the limbic system and stands to integrate exteroceptive information with interoceptive states underlying social interactions. Review of the pertinent literature shows that word comprehension and conduct impairments caused by temporopolar strokes and temporal lobectomy are far less severe than those seen in temporopolar atrophies. One explanation for this unexpected discrepancy invokes the miswiring of residual temporopolar neurons during the many years of indolently progressive neurodegeneration. According to this hypothesis, the temporopolar regions become not only dysfunctional but also sources of aberrant outputs that interfere with the function of areas elsewhere in the language and paralimbic networks, a juxtaposition not seen in lobectomy or stroke.

Breast adenocarcinoma is a leading cause of death in females worldwide. A broad spectrum of genetic and epigenetic alterations has been already identified and reported in millions of examined cancerous substrates, evidence of a high-level genomic heterogeneity that characterizes these malignancies. Concerning epigenetic changes and imbalances that critically affect progression and prognosis in the corresponding patients, DNA methylation, histone modifications (acetylation), micro-RNAs (miRs) alterations and chromatin re-organization represent the main mechanisms. Referring to DNA methylation, promoter hyper-hypo methylation in critical tumour suppressor and oncogenes is implicated in normal epithelia transformation to their neoplastic and finally malignant cyto-phenotypes. The current review is focused on the different methylation patterns and mechanisms detected in breast adenocarcinoma and their impact on the corresponding groups of patient response to specific chemotherapeutic regimens and life span prognosis.

Root caries is a growing problem for the worldwide aging population. Silver diamine fluoride (SDF) contains high concentrations of silver and fluoride ions, which prevents and arrests root caries, as well as dentin caries in the primary teeth of young children. Unlike other fluoride products that mainly reduce the formation of new carious lesions, 38% SDF is an effective agent that can efficiently arrest the carious process, remineralize the decayed dental tissues, and protect the tooth structure against the formation of new caries lesions. The use of SDF can result in more caries-resistant tooth structures. Despite these merits, its clinical disadvantages are the deep penetration of silver ions and sequential formation of silver compounds, which cause esthetic concern due to the discoloration and impaired efficacy of dentin bonding after using SDF. Thus, this narrative review, by addressing the primary experimental results and clinical applications of SDF on root caries, proposes management methods for root caries in conjunction with the application of SDF. We propose a two-visit treatment protocol to take advantage of the SDF application for root surface caries and utilize the discoloration caused by SDF.

The outbreaks of infectious diseases that spread across countries have generally existed for centuries. An example is the occurrence of the COVID-19 pandemic in 2020, which led to the loss of lives and economic depreciation. One of the essential ways of handling the spread of viruses is the discovery and administration of vaccines. However, the major challenges of vaccination programs are associated with the vaccine cold chain management and cold storage facilities. This paper discusses how vaccine cold chain management and cold storage technology can address the challenges of vaccination programs. Specifically, it examines different systems for preserving vaccines in either liquid or frozen form to help ensure that they are not damaged during distribution from manufacturing facilities. Furthermore, A vaccine is likely to provide very low efficacy when it is not properly stored. According to preliminary studies, the inability to store vaccine properly is partly due to the incompetency of many stakeholders, especially in technical matters. The novelty of this study is to thoroughly explore cold storage technology for a faster and more comprehensive vaccine distribution hence it is expected to be one of the reference and inspiration for stakeholders.

Objectives: The aim of this systematic review was to evaluate the possible impacts of COVID-19 on oral and maxillofacial surgery practice, as well as the protocols employed by oral and maxillofacial surgeons to minimize the risks of contamination. Methods: Searches were performed in different databases up to 15 March 2021. Articles related to oral surgery dynamics within the context of the COVID-19 pandemic were included. The articles were considered eligible if they met the following inclusion criteria: observational studies that provided recommendations regarding maxillofacial surgery measures during the COVID-19 pandemic and that analyzed the risk of contamination of patients/professionals with SARS-CoV-2. Results: Seven studies met the inclusion criteria and were selected for the present systematic review. Demands for personal protective equipment increased significantly, with studies reporting the scarcity of fundamental equipment such as FFP2/N95 masks. Significant changes in the infrastructure of outpatient, surgical and inpatient units and in the care protocols themselves were observed. Conclusion: The COVID-19 pandemic particularly affected the routine of oral and maxillofacial surgery residents. Several additional recommendations for surgical practice or for the surgical team were evaluated and discussed, such as performing primarily urgent and emergency surgeries, remote patient care and screening, postponing elective surgeries, and new teaching methods in oral and maxillofacial surgery residency programs. In addition, screening of patients and of the surgery team for COVID-19 is strongly recommended.

Introduction: Skin is the largest organ of the human body protecting the underlying organs and tissues from any foreign attack. Any damage caused in the skin may sometimes result in serious consequences within the internal body tissues. Burn is one such issue that damages the layers of the skin and thereby making the skin vulnerable and prone to any foreign matter entering and causing serious diseases. Methods: An online literature assessment was steered for the lipid nanoparticles, burn wound treatments, and different types of nanoformulation. Appropriate information was taken from different electronic scientific databases such as Web of Science, Elsevier, Science Direct, Springer, PubMed, Google Scholar etc. Additional data was summarized from textbooks, local prints and scripts. Results: Recent innovations and developments in nanotechnology-based drug delivery systems have shown promising results in minimizing the drawbacks associated with conventional therapies. Lipid based nanoparticles possess capabilities to deliver active agents to their target site without the possibility of degradation. Conventional therapy of burn wound is costly and the treatment is long lasting, making the patient uncomfortable. Moreover, it also doesn’t yield satisfactory results or narrow effects. Encapsulation of bioactives inside the lipid core protects the active entity from pH and enzymatic degradations. Conclusion: This review highlights the drawbacks associated with conventional dosage forms. A lot of consideration is focused on the advancement of nanomaterials using innovative methods in wound care for treating burn wounds with a faster healing effect. This review article highlights recent developments in lipid based nanoformulations for the treatment of burn wound injury.

Mounting evidence has demonstrated that a myriad of developmental signaling pathways, such as the Wnt, Notch, Hedgehog and Hippo, are frequently deregulated and play a critical role in regulating cancer stem cell (CSC) activity in human cancers, including gynecologic malignancies. In this review article, we describe an overview of various signaling pathways in human cancers. We further discuss the developmental roles how these pathways regulate CSCs from experimental evidences in gynecologic cancers. Moreover, we mention several compounds targeting CSCs in gynecologic cancers to enhance the treatment outcomes. Therefore, these signaling pathways might be the potential targets for developing targeted therapy in gynecologic cancers.

Genetic testing is increasingly used in the workup and diagnosis of kidney disease and kidney-related disorders of undetermined cause. Out-of-pocket costs for clinical genetic testing have become affordable, and logistical hurdles overcome. The interest in genetic testing may stem from the need to make or confirm a diagnosis, guide management, or the patient’s desire to have a more informed explanation or prognosis. This poses a challenge for providers who do not have formal training in the selection, interpretation, and limitations of genetic tests. In this manuscript, we provide detailed discussion of relevant cases in which clinical genetic testing using a kidney gene panel was applied. The cases demonstrate identification of pathogenic variants for monogenic diseases—contrasting them from genetic risk alleles—and bring up diagnostic limitations and diagnostic utility of these tests in nephrology. This review aims to guide clinicians in formulating pretest conversations with their patients, interpreting genetic variant nomenclature, and considering follow-up investigations. Although providers are gaining experience, there is still risk of testing causing more anxiety than benefit. However, with provider education and support, clinical genetic testing applied to otherwise unexplained kidney-related disorders will increasingly serve as a valuable diagnostic tool with the potential to reshape how we consider and treat many kidney-related diagnoses.