Risk of Gynecological Cancers in Women With Polycystic Ovary Syndrome and the Pathophysiology of Association.

Polycystic ovary syndrome (PCOS) is an endocrine disorder increasingly affecting women in the reproductive age group. The women usually present with menstruation irregularities, hirsutism, weight gain, and acne. There has been ongoing research about the increased risk of gynecological cancers in women with polycystic ovary syndrome compared to those without it. This review aimed to understand the risk of gynecological cancers, endometrial, ovarian, and breast cancer in PCOS, and to study in detail the underlying mechanisms involved. We searched PubMed and Google Scholar databases for studies and selected 10 articles from a total of 19,388 relevant articles. We found an increased risk of endometrial cancer in women with PCOS whereas the risk of ovarian and breast cancer was not increased. A recent study has even reported a reduced risk of ovarian cancer in genetically predicted PCOS. In understanding various medical conditions possibly leading to cancer in these women we found that hyperandrogenism, hyperinsulinemia, unopposed estrogen action, chronic inflammation, and dyslipidemia were major contributors. There is a need for more large-scale cohort studies which will take into consideration other factors leading to cancers in women with PCOS, such as smoking, alcohol, and family history, to substantiate the significance of these associations further. The interventions used to treat PCOS might also affect the risk of cancer and require further probing. This review is an attempt to analyze the risk of cancers of the reproductive system in females with PCOS in coherence with understanding the mechanisms leading to the respective cancers.

Modification of Orticochea Three-Flap Technique for Reconstruction of Lateral Forehead Defect.

Surgical defects in temporo-parieto-frontal region are challenging to reconstruct (Ransom in Arch Facial Plast Surg, 2012. 10.1001/archfacial.2012.7). The size and site of the defect determines its mode of reconstruction (Ransom in Arch Facial Plast Surg, 2012. 10.1001/archfacial.2012.7). A 60-year-old lady presented with basal cell carcinoma (BCC) over the skin of the right temporal region. She underwent wide excision of the lesion resulting in a moderate sized skin and soft tissue defect. Reconstruction of the defect was challenging owing to the size not amenable for primary closure, lack of pliability of adjoining soft tissue and proximity to structures of aesthetic significance. In order to achieve a functional and aesthetic reconstruction, a modified Orticochea three-flap reconstruction technique was used. This case report describes in detail the surgical procedure and outcome.

Zika Virus: A Systematic Review of Teratogenesis, Congenital Anomalies, and Child Mortality.

Zika virus infection (ZIKV) was one of the most catastrophic epidemics. ZIKV in nonpregnant women is mild and sometimes asymptomatic. However, infection during pregnancy leads to congenital malformations in the fetus, while maternal signs of infection are preceded by a rash. The maternal-fetal infection begins with a rash that occurs early during pregnancy. The most severe pathologies were related to the first trimester of gestation, including microcephaly, musculoskeletal, genitourinary, craniofacial, ocular, and pulmonary manifestations. The prognosis may not be encouraging. Herd immunity increases CD8+ (cytotoxic T-lymphocytes) earlier and decreases in the resolution phase. However, CD4+ (T-helper cells) remains higher after infection. Recent ongoing vaccine development shows good immunity, control of the vector (Aedes mosquitoes), and treatment. ZIKV, anomalies, mortality, herd immunity, and vaccine were our main keywords. This systematic review demonstrates the teratogenesis of ZIKV in children, congenital anomalies, mortality, and a view of the future and behavior of ZIKV.

The Efficacy of Safinamide in the Management of Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is a chronic neurodegenerative disease that is challenging to treat due to its progressive nature and its weaning response to therapy. Safinamide, a monoamine oxidase type-B inhibitor (MAOB-I), has shown promise in managing dyskinesias caused by levodopa (L-dopa), carbidopa, and PD features such as pain and depression. This systematic review aimed to evaluate safinamide's efficacy as a monotherapy and an add-on in tackling these issues. We composed this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Our group searched the following databases: Manchester University Library, ScienceDirect, Google Scholar, PubMed, PubMed Central, and MedLine for articles produced in the last ten years using various search terms and criteria, which we outlined in the search strategy and eligibility criteria sections. We excluded 722 out of the initially screened 730 records for multiple reasons, such as titles and abstracts being irrelevant to the topic, articles without free full access, articles originally not in the English language, and articles that did not score 70% or above on their respective quality assessment tools. The studies explored supported safinamide's use in managing motor fluctuations, pain, depression, and improving patients' quality of life.

A Systematic Review of the Gastrointestinal Microbiome: A Game Changer in Colorectal Cancer.

Colorectal cancer (CRC) is a malignant condition of the colon and rectum. Generally, malignancies constitute a significant health threat to humans, and the result can be devastating. CRC is no exception. The gastrointestinal (GI) microbiome has long been suspected of impacting CRC. This review seeks to explore whether there is a connection between the two or not. For screening purposes, relevant articles were culled from various databases using key terms and phrases. Following a thorough search, the inclusion and exclusion criteria were applied, and a quality assessment was conducted. The articles retained were comprehensively studied, and revealed imbalances of the GI microbiome do indeed exhibit an association with CRC.

Treatment Options That Reduce the Duration of Sickle Cell Vaso-Occlusive Crises: A Systematic Review.

Most patients with sickle cell disease (SCD) seek hospital care because of pain symptoms. While some patients opt to treat themselves at home, some prefer to seek treatment in a hospital setting. There are, however, some patients with more complicated effects of the disease who seek treatment so often that they have been termed "super-users." This paper seeks to determine, across the board, the treatments available for vaso-occlusive crisis (VOC), the most common complication of SCD. Due to the frequency and unpredictable nature of VOC, it is no surprise that the lives of so many patients dealing with SCD are constantly disrupted by this complication. Treatments that reduce the frequency of VOC and the need for hospital admissions will help these patients find some semblance of balance in their quality of life.

Effectiveness of Prophylactic Interventions in Neurogenic Heterotopic Ossification (NHO): A Systematic Review.

Neurogenic heterotopic ossification (NHO) is the formation of mature lamellar bone in peri-articular tissues following a neurological insult, most commonly traumatic brain injury (TBI) or spinal cord injury (SCI). NHO is a debilitating condition associated with significant morbidity and reduced quality of life. However, its pathophysiology remains poorly understood. While surgery is the mainstay of treatment once NHO has been diagnosed, prophylactic options are limited and not well studied. This review aimed to determine the efficacy of various interventions used in the primary prevention of NHO. We conducted an electronic literature search using five databases (PubMed, Embase, ScienceDirect, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) for records published until April 10, 2022. We identified 2,610 potentially eligible records across all databases. Nine reports met our eligibility criteria and were included in this review. Four were clinical trials (three randomized control trials, one nonrandomized trial), four were observational studies, and one was a systematic review/meta-analysis. The medications/interventions used included: warfarin, pulse low-intensity electromagnetic field therapy (PLIMF), bisphosphonates, and nonsteroidal anti-inflammatory drugs (NSAIDs). We did not find conclusive evidence to recommend the use of bisphosphonates and warfarin in the prevention of NHO. On the contrary, we found NSAIDs and PLIMF as effective prophylactic options based on the results of high-quality randomized control trials. Further prospective randomized studies with prolonged follow-ups are needed to confirm the long-term efficacy of these preventive interventions.

Submental Intubation in Maxillofacial Procedures: A More Desired Approach Than Nasotracheal Intubation and Tracheostomy.

To achieve adequate airway management in maxillofacial procedures, the right intubation technique should be employed. This is because the surgeons and the anesthesiologists will need to work in the same surgical field to ensure a successful procedure. The type of intubation method used can either complicate either's role or pose some difficulties in the surgery itself. Nasotracheal intubation and orotracheal intubation may often be contraindicated in different types of maxillofacial surgeries and due to the complications associated with a tracheostomy, this method is often utilized as a last resort. Submental intubation has become very popular and favored alternative and has been associated with fewer complications. This literature review was conducted to explore the indications, complications, and contraindications of the different intubation methods. Sources were gathered from PubMed Central, PubMed, and Google scholar and included articles published between 2012 and 2022. A mix of literature reviews, case base studies, retrospective studies, prospective studies, and a few systematic reviews were examined. It was found that the use of submental intubation was preferred due to its less invasive nature, minimal intraoperatively and postoperatively complications, and greater patient compliance compared to tracheostomy. In addition, it is the best method when Nasotracheal intubation is contraindicated.

Just When We Thought That COVID Was Over: A Systematic Review.

As the globe continues to grapple and scuffle with new emerging strains of COVID every day, a set of recovered patients continue to show persistent enervating symptoms. Many patients never fully recovered after COVID and had neurological and psychiatric symptoms for weeks or months. The emphasis of our study is on these long haulers, particularly on the two critical organ systems of the body, i.e., the central nervous system and the muscular system. Depending upon the severity of the disease, many signs and symptoms continue to linger, ranging from weeks to months. A total of 29 studies are included in our review after thorough screening, application of inclusion and exclusion criteria, and quality appraisals. The total number of patients included is 6012. We found many long-term effects, but the emphasis of our study continued to remain on the two main organ systems that resulted in prolonged COVID with debilitating symptoms and thus affected the quality of life of these patients. Various factors and underlying pathophysiologic manifestations result in the predominance of these signs and symptoms. Furthermore, the patient's underlying medical conditions and other environmental factors may add to it. More focus is required on the quality of life post-COVID, and this requires a team of specialists. There are still many unanswered questions like which ethnicity is affected more, why females are more prone to the long symptoms, and the effects of various treatments on the long-term signs and symptoms.

A Systematic Review on the Efficacy and Safety of Selective Serotonin Reuptake Inhibitors in Gastrointestinal Motility Disorders: More Control, Less Risk.

Gastrointestinal motility disorders have been thought to occur due to an imbalance in the interaction of the gut-brain axis, which is regulated by serotonin. This recent discovery can be exploited to find newer therapeutic agents such as selective serotonin reuptake inhibitors for functional gastrointestinal disorders. PubMed, PubMed Central (PMC), and Medline databases were used to obtain the data. Meta-analyses, systematic reviews, randomized control trials, and reviews were included and analyzed in the data. Of the 19240 studies, 23 were extracted, and after appropriate quality assessment, they were utilized in this systematic review. They included two meta-analyses, four systematic reviews, two randomized control trials, and 15 review articles. The systematic review focuses on the efficacy of selective serotonin reuptake inhibitors (SSRIs) as compared to other treatment modalities for disorders of gut-brain interaction. It explores various studies analyzing SSRIs for their mechanism of action, their desirable effects for treating irritable bowel syndrome, and their tolerability in patients. SSRIs are effective and safe in treating overall symptoms of gastrointestinal motility disorders, particularly constipation-predominant disorders. They seem to have a better side effect profile than other drugs. This should encourage physicians to prescribe SSRIs early on in the disease.

Oxandrolone Efficacy in Wound Healing in Burned and Decubitus Ulcer Patients: A Systematic Review.

Wounds with delayed or impaired healing represent a considerable challenge in medical practice. These patients develop a sustained hypermetabolic and catabolic state, directly impacting the wound healing process. The use of oxandrolone has been studied to control this metabolic imbalance and protect lean body mass as a beneficial resource in wound healing. This systematic review aims to analyze previously conducted randomized controlled trials to evaluate the evidence of the applicability of oxandrolone therapy. We compared its use in adult patients with burns and adult patients with pressure ulcers in terms of wound healing and healing time of the skin graft donor site in days. The digital searches were done from March 23-28, 2022, within the databases: Google Scholar, PubMed/MEDLINE, and EBSCO (Elton B. Stephens Company). Data from six studies were analyzed and included in this review. Analysis of the available data demonstrated a significant advantage in skin healing using oxandrolone in adult burn patients as an adjunct. For adult patients with pressure ulcers, the drug showed no benefit on wound healing and skin graft site healing. Importantly, we found only one study evaluating the use of oxandrolone in patients with decubitus ulcers that met our eligibility criteria, and the certainty of the evidence was low. Thus, further prospective randomized studies with larger samples and standard wound care protocols are needed to produce more solid results, allowing more definitive conclusions to be made on this theme.

Imidazole-Mediated Dual Location Disassembly of Acid-Degradable Intracellular Drug Delivery Block Copolymer Nanoassemblies.

Acid-degradable (or acid-cleavable) polymeric nanoassemblies have witnessed significant progress in anti-cancer drug delivery. However, conventional nanoassemblies designed with acid-cleavable linkages at a single location have several challenges, such as, sluggish degradation, undesired aggregation of degraded products, and difficulty in controlled and on-demand drug release. Herein, a strategy that enables the synthesis of acid-cleavable nanoassemblies labeled with acetaldehyde acetal groups in both hydrophobic cores and at core/corona interfaces, exhibiting synergistic response to acidic pH at dual locations and thus inducing rapid drug release is reported. The systematic analyses suggest that the acid-catalyzed degradation and disassembly are further enhanced by decreasing copolymer concentration (i.e., increasing proton/acetal mole ratio). Moreover, incorporation of acid-ionizable imidazole pendants in the hydrophobic cores improve the encapsulation of doxorubicin, the anticancer drug, through π-π interactions and enhance the acid-catalyzed hydrolysis of acetal linkages situated in the dual locations. Furthermore, the presence of the imidazole pendants induce the occurrence of core-crosslinking that compensates the kinetics of acetal hydrolysis and drug release. These results, combined with in vitro cell toxicity and cellular uptake, suggest the versatility of the dual location acid-degradation strategy in the design and development of effective intracellular drug delivery nanocarriers.

Synthesis and characterization of an injectable microparticles integrated hydrogel composite biomaterial: In-vivo biocompatibility and inflammatory arthritis treatment.

Polymeric hydrogels and microparticles have been widely used for localized drug delivery applications for the treatment of arthritis. Nonetheless, owing to initial burst drug release, non-specific biodistribution and low retention time at the target site in body, these polymeric drug delivery systems have been found with low in-vivo performance. Hence, the above limitations need to be resolved by designing a smart novel drug delivery system which is the current need in biomedicine. Herein, a novel localized injectable thermoresponsive microparticles embedded hydrogel composite drug delivery system has been developed for the treatment of inflammatory arthritis. In the current study, methotrexate (MTX) loaded alginate microparticles (MTX-Microparticles) are embedded into thermoreversible hydrogel matrix (MTX-MPs-H) prepared by physical blending of sodium hyaluronate and methylcellulose (SHMC). Microparticles-hydrogel composite system exhibited appropriate in-vitro thermoreversibility (sol at 4 °C and gel at 37 °C), biocompatibility (>80 %), hemocompatibility, and controlled drug release profile. The in-vivo biocompatibility studies for 10 days revealed that composite system is non-toxic in nature. The developed MTX-MPs-H composite drug delivery system effectively decreased the swelling/ inflammation of the arthritis affected paw in wistar rats in comparison to only alginate microparticles and pure MTX up to 30 days.

Dual-Location Dual-Acid/Glutathione-Degradable Cationic Micelleplexes through Hydrophobic Modification for Enhanced Gene Silencing.

Gene therapy holds great promise for the treatment of acquired genetic disorders such as cancer with reduced side effects compared to chemotherapy. For gene therapy to be successful, it is crucial to develop efficient and nontoxic gene carriers to overcome the poor in vivo stability and low cellular uptake of nucleic acid-based therapeutic agents. Here, we report a new and versatile approach exploring a combination of hydrophobic modifications and dual-stimuli-responsive degradation (SRD) for controlled gene delivery with amphiphilic block copolymer-based nanocarriers. The block copolymer, synthesized by atom transfer radical polymerization, is designed with an acid-labile acetal linkage at the block junction and a pendant disulfide group in the hydrophobic block. The incorporation of labile linkages enables both disulfide-core-cross-linking and dual-location dual-acid/reduction-responsive degradation (DL-DSRD). Furthermore, the disulfide linkages integrated as hydrophobic moieties facilitate the nucleic acids to condense into nanometer-sized micelleplexes through electrostatic interactions of pendant dimethylamino groups with the anionic phosphate groups of the nucleic acids. Our preliminary results demonstrate that the DL-DSRD approach through hydrophobic modification is a robust platform in the development of gene delivery systems with enhanced colloidal stability, reduced cytotoxicity, and improved gene transfection efficiency.

Dual Reduction/Acid-Responsive Disassembly and Thermoresponsive Tunability of Degradable Double Hydrophilic Block Copolymer.

We report a thermoresponsive double hydrophilic block copolymer degradable in response to dual reduction and acidic pH at dual locations. The copolymer consists of a poly(ethylene oxide) block covalently connected through an acid-labile acetal linkage with a thermoresponsive polymethacrylate block containing pendant oligo(ethylene oxide) and disulfide groups. The copolymer undergoes temperature-driven self-assembly in water to form nanoassemblies with acetal linkages at the core/corona interface and disulfide pendants in the core, exhibiting dual reduction/acid responses at dual locations. The physically assembled nanoaggregates are converted to disulfide-core-crosslinked nanogels through disulfide-thiol exchange reaction, retaining enhanced colloidal stability, yet degraded to water-soluble unimers upon reduction/acid-responsive degradation. Further, the copolymer exhibits improved tunability of thermoresponsive property upon the cleavage of junction acetal and pendant disulfide linkages individually and in combined manner. This work suggests that dual location dual reduction/acid-responsive degradation is a versatile strategy toward effective drug delivery exhibiting disulfide-core-crosslinking capability and disassembly as well as improved thermoresponsive tunability.

Mandibulotomy Approach for Resection of Maxillary Tumours: A Clinical Review.

PURPOSE: The objective of this study was to assess the accessibility in the resection of maxillary tumours, resection margin status, and morbidity following maxillectomy through lip split with paramedian mandibulotomy approach. MATERIALS AND METHODS: A retrospective review of 20 consecutive patients who underwent maxillectomy with resection of primary tumours through lip split mandibulotomy approach with supraomohyoid neck dissection for maxillary tumours between 2008 and 2016. Patients details including the tumours site, extension and neck node involvement. were recorded. Resection technique, status of surgical resected margins was also discussed. Disease status was obtained from patients follow up records. Morbidity was assessed at mandibulotomy site in terms of infection, osteotomy healing, neural disturbance and mouth opening. The institutional research committee approval was taken for this study. RESULTS: All patients underwent adequate en bloc resection of the tumours, except in two patients in whom superior margins was positive. Osteotomy site healed well in our all patients except in one patient in whom there was infection at the osteotomy site during post radiation therapy. Minimal neural morbidity was encountered in four patients (three patients had lingual nerve hypothesia and two patients had inferior alveolar nerve hypothesia) which recovered in all four patients, over the 6th month post-operative period. Post-operative interincisal distance was satisfactory with a mean of 30.5 mm. CONCLUSION: Mandibulotomy with lip split is considered to be an ideal approach to access tumours of maxilla and its adjacent structures, SOHND with level III clearance. This approach provide excellent accessibility for en bloc resection of operable maxillary tumours with good outcome of resultant scar and minimal morbidity.

PLA-Based Triblock Copolymer Micelles Exhibiting Dual Acidic pH/Reduction Responses at Dual Core and Core/Corona Interface Locations.

Polylactide (PLA)-based amphiphilic block copolymers and their nanoassemblies designed with stimuli-responsive degradation (SRD) hold great potential as promising candidates for tumor-targeting drug delivery. However, most of the smart PLA-based nanoassemblies are designed to respond to a single stimulus (typically reduction or acidic pH). Herein, a new strategy is reported to synthesize PLA-based block copolymer micelles exhibiting dual SRD at dual locations (DL-DSRD). The strategy utilizes a combination of ring opening polymerization, controlled radical polymerization, and facile coupling reactions to synthesize an ABA-type PLA-based triblock copolymer with a hydrophilic polymethacrylate (A) and PLA (B) blocks. Incorporation of an acidic pH-responsive ketal linkage in the center of PLA block and reduction-responsive disulfide linkages at PLA/hydrophilic polymethacrylate blocks ensure the formation of smart nanoassemblies featured with ketal linkages in the PLA cores and disulfide linkages at core/corona interfaces, thus attaining DL-DSRD. Such dual acidic pH/reduction-responses at dual locations lead to not only shedding of coronas at interfaces but also destabilization of cores, resulting in the synergistic and accelerated release of encapsulated model drugs, compared with the single stimulus systems. These results, along with lower cytotoxicity, suggest that DL-DSRD strategy can offer versatility in the development of tumor-targeting drug delivery nanocarriers.

Methotrexate loaded gellan gum microparticles for drug delivery.

Recently, polysaccharides based microparticles have been found to offer an attractive potential as a carrier in drug delivery field. In this study, bare gellan gum microparticles (GG MPs) and methotrexate (MTX) loaded gellan gum microparticles (MTX-GG MPs) prepared by using simple water-in-oil (W/O) emulsion solvent diffusion method. The developed microparticles (MPs) were found discretely distributed in a spherical shape. MTX has been encapsulated in microparticles with 84.8 ±â€¯1.68% encapsulation efficiency (%EE) and 6.45 ±â€¯0.07% loading capacity (%LC). The Fourier Transform Infrared Spectroscopy (FTIR) characterization of the MPs clearly indicated the physical encapsulation of MTX into polymeric matrix of MPs. Thermogravimetric analysis (TGA) characterization showed slightly higher thermal stability of MTX-GG MPs in comparison to the GG MPs. In vitro release study of MTX-GG MPs showed 84% drug release within 24 h. The hemolysis study of GG MPs and MTX-GG MPs on human red blood cells (RBCs) showed <1.0% hemolysis. The cell viability studies on L929 showed GG MPs, and MTX-GG MPs are biocompatible.

Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation.

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca2+. The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11µm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations.