Mesenchymal stem cells and their potential therapeutic benefits and challenges in the treatment and pathogenesis of gastric cancer.

Mesenchymal stem/stromal cells (MSCs) are acknowledged for their remarkable ability to undergo differentiation into various cell types. In addition, they exhibit anti-tumor characteristics, prompting endeavors to modify MSCs for employment in cancer therapies. On the contrary, it is imperative to recognize that MSCs have been extensively linked to pathways that facilitate the advancement of tumors. Numerous research studies have sought to modify MSCs for clinical application; however, the outcomes have been ambiguous, potentially due to the heterogeneity of MSC populations. Furthermore, the conflicting roles of MSCs in suppressing and promoting tumor growth present a challenge to the appropriateness of their use in anti-cancer therapies. Currently, there exists a lack of comprehensive comprehension concerning the anti-tumor and pro-tumor characteristics of MSCs for gastric cancer (GC). This article discusses the influence of MSCs on GC, the underlying mechanisms, the origins of MSCs, and their effects. This review article also elucidates how MSCs exhibit dual characteristics of promoting and inhibiting tumor growth. Hence, it is of utmost importance that clinical inquiries aimed at utilizing MSCs as a therapeutic intervention for cancer consider the potentiality of MSCs to accelerate the progression of GC. It is crucial to exercise caution throughout the process of developing MSC-based cellular therapies to enhance their anti-cancer attributes while simultaneously eliminating their tumor-promoting impacts.

Unilateral avascular necrosis of the right hip in an HIV patient with tearing of the rectus femoris and adductor longus muscles.

A man in his 20s with a medical history of syphilis, chlamydia and HIV presented to the emergency department (ED) with 2 months of right hip pain and was found to have advanced avascular necrosis (AVN) of the right femoral head with secondary haemorrhage. The patient lacked the common risk factors of AVN in patients with HIV (PWH): ≥10 years of HIV diagnosis, extended duration on highly active antiretroviral therapy, trauma, corticosteroid use, alcohol abuse, systemic lupus erythematosus, obesity, smoking and dyslipidaemia. Given the extensive destructive changes in the hip joint and muscles, a right hip resection arthroplasty was performed, and the patient recovered well postoperatively. This case presents a learning opportunity for understanding bone pathologies in PWH and offers clinical guidance for the management of HIV-infected patients with a focus on optimising bone health.

Understanding role of pesticides in development of Parkinson's disease: Insights from Drosophila and rodent models.

Parkinson's disease is a neurodegenerative illness linked to ageing, marked by the gradual decline of dopaminergic neurons in the midbrain. The exact aetiology of Parkinson's disease (PD) remains uncertain, with genetic predisposition and environmental variables playing significant roles in the disease's frequency. Epidemiological data indicates a possible connection between pesticide exposure and brain degeneration. Specific pesticides have been associated with important characteristics of Parkinson's disease, such as mitochondrial dysfunction, oxidative stress, and α-synuclein aggregation, which are crucial for the advancement of the disease. Recently, many animal models have been developed for Parkinson's disease study. Although these models do not perfectly replicate the disease's pathology, they provide valuable insights that improve our understanding of the condition and the limitations of current treatment methods. Drosophila, in particular, has been useful in studying Parkinson's disease induced by toxins or genetic factors. The review thoroughly analyses many animal models utilised in Parkinson's research, with an emphasis on issues including pesticides, genetic and epigenetic changes, proteasome failure, oxidative damage, α-synuclein inoculation, and mitochondrial dysfunction. The text highlights the important impact of pesticides on the onset of Parkinson's disease (PD) and stresses the need for more research on genetic and mechanistic alterations linked to the condition.

Sensitivity Profile of Fosfomycin, Nitrofurantoin, and Co-trimoxazole Against Uropathogens Isolated From UTI Cases in a Secondary Care Center, KSA.

Background Fosfomycin, nitrofurantoin, and co-trimoxazole are cheap and effective first-line oral antimicrobials in cases of uncomplicated cystitis in males and non-pregnant females. Fosfomycin and nitrofurantoin are called urinary antiseptics because these two drugs are primarily excreted in the kidney and concentrated in the urine without systemic effect. The present study was designed to evaluate the in vitro activities of fosfomycin, nitrofurantoin, and co-trimoxazole against uropathogens isolated at King Khalid Hospital Al-Majmaah, KSA. Methods The study was conducted at the King Khalid Hospital Al Majmaah, KSA, from September 1, 2021, until February 28, 2022. The patients' urine samples were inoculated on the Cystein Lactose Electrolytes Deficient (CLED) medium, and uropathogens were isolated. The organisms' identification and sensitivity testing against cotrimoxazole, fosfomycin, and nitrofurantoin was conducted using a Microscan automated analyzer, the MicroScan WalkAway Beckman Coulter, Sacramento, CA, USA. Results The study comprised non-repeat 137 patients who were either admitted to the hospital or treated as outpatients, yielding a total of 147 isolates. Nitrofurantoin showed a lower resistance rate, around 20% (n = 29), followed by fosfomycin at 23% (n = 34). The resistance rate of cotrimoxazole was 43% (n = 63). Overall, nitrofurantoin and fosfomycin showed relatively lower resistance against all isolates. Conclusions Being cheap and effective, we propose that fosfomycin and nitrofurantoin be used as first-line treatments in patients presenting with uncomplicated UTIs.

Preparation of novel S-allyl cysteine chitosan based nanoparticles for use in ischemic brain treatment.

Objective: To enhance the brain bioavailability of S-allyl-l-cysteine (SC) by developing novel S-allyl-l-cysteine chitosan nanoparticles (SC CS NPs) and examining the quantity of SC by developing a novel method of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in ischemic rat brain treatment. Methods: The ionotropic gelation method was used to develop S-allyl cysteine-loaded CS NPs. The 4-factor, 5-level central composite design was optimized to determine the effect of independent variables, i.e., particle size, polydispersity index (PDI), zeta potential, EE, and loading capacity, together with their characterization, followed by drug release and intranasal permeation to enhance the brain bioavailability and examination of their neurobehavioral and biochemical parameters with their histopathological examination. Results: SC CS NPs were optimized at the particle size of 93.21 ± 3.31 nm (PDI: 0.317 ± 0.003), zeta potential of 44.4 ± 2.93, and drug loading of 41.23 ± 1.97% with an entrapment efficiency of 82.61 ± 4.93% having sustain and controlled release (79.92 ± 3.86%) with great permeation (>80.0%) of SC. SC showed the retention time of 1.021 min and 162.50/73.05 m/z. SC showed good linearity in the range of 5.0-1300.0 ng mL-1, % inter-and-intraday accuracy of 96.00-99.06% and CV of 4.38-4.38%. We observed significant results, i.e., p < 0.001 for improved (AUC)0-24 and Cmax delivered via i.v. and i.n. dose. We also observed the highly significantly observations of SC CS NPs (i.n.) based on their treatment results for the biochemical, neurobehavioral, and histopathological examination in the developed ischemic MCAO brain rat model. Conclusion: The excellent significant role of mucoadhesive CS NPs of SC was proven based on the enhancement in the brain bioavailability of SC via i.n. delivery in rats and easy targeting of the brain for ischemic brain treatment followed by an improvement in neuroprotection based on a very small dose of SC.

Spontaneous secondary pneumothorax due to cannabis-induced bullous lung disease: a case report.

Marijuana use has grown rapidly in the last decade with a prevalence greater than that of cocaine and opioids. With its increasing recreational and medical use, potential adverse outcomes from heavy use may be associated with bullous lung disease and spontaneous pneumothorax. This case report has been reported in line with the SCARE Criteria. Case presentation: The authors describe a case of an adult male with a past medical history of spontaneous pneumothorax and long-standing marijuana use presenting with dyspnoea who was found to have a secondary spontaneous pneumothorax requiring invasive treatment. Clinical discussion: The aetiology of lung injury due to heavy marijuana smoke may be from direct tissue injury from inhaled irritants and the method of which marijuana smoke is inhaled compared with tobacco smoke. Conclusion: Chronic marijuana use should be considered when evaluating structural lung disease and pneumothorax in the setting of minimal tobacco use.

Adult-Onset Immunoglobulin A Vasculitis With Renal Involvement.

A 50-year-old male presented with worsening bilateral lower extremities swelling for a month, associated with a purpuric rash over bilateral upper and lower extremities, joint pain over bilateral hands and ankles, and intermittent generalized abdominal pain. Physical examination was notable for pitting edema in bilateral lower extremities and palpable, non-blanching purpuric rashes and crusts, joint tenderness over bilateral hands/wrists/ankles, and mild generalized abdominal tenderness. Laboratory tests were remarkable for sub-nephrotic range proteinuria and microscopic hematuria. The skin biopsy revealed leukocytoclastic vasculitis. Renal biopsy showed mild mesangial expansion and immunoglobulin A (IgA)-dominant mesangial deposits. The patient was diagnosed with IgA vasculitis (IgAV) nephritis (IgAVN) and was subsequently treated with oral prednisone 80 mg daily for seven days followed by slow tapering doses, oral lisinopril 2.5 mg daily, and oral furosemide 40 mg daily. At the one-month follow-up as an outpatient, his skin rash and lower extremity swelling had resolved along with an improvement of proteinuria.

Assessing the Relationship between Socioeconomic Status, Race, and Psychological Distress in Cancer Survivors: A Population Based Study.

Psychological distress is more common in cancer survivors than the general population, and is associated with adverse outcomes. This cross-sectional study aimed to assess the relationship between socioeconomic status (SES), race and psychological distress, using data from a nationally representative sample of cancer survivors in the United States. Outcomes of interest were mild, moderate, and severe psychological distress as assessed by the Patient Health Questionnaire-4 (PHQ-4). In our univariate model, there was no statistically significant difference in the PHQ-4 scores of Caucasian and African American respondents. On the other hand, a lower SES correlated with a higher likelihood of psychological distress, and this persisted in our multivariate model. This study brings additional awareness to the negative impact of a lower socioeconomic status on mental health outcomes in cancer survivors, and further highlights the importance of the timely identification and screening of individuals at a high risk of psychological distress, in order to limit missed opportunities for relevant mental health interventions in this population.

Paroxysmal nocturnal hemoglobinuria clone in a patient with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia which is clonal in nature due to somatic mutation. PNH may evolve to aplastic anemia, and more rarely, to a myelodysplastic syndrome or to AML. The literature review showed that AML is derived from the PNH clone as the leukemic cells lack the expression of glycosylphosphatidylinositol-linked proteins and PNH phenotype disappeared with the onset of acute leukemia. Herein, we report an unusual presentation of the coexistence of two clonal disorders PNH and APL. Our case contributes to the literature that AML in the setting of PNH is a separate disorder.

Sphenoclival Intraosseous Lipoma: A Typical Lesion at an Atypical Location.

In this report, we present the case of a rare tumor in the sphenoclival region and discuss the potential pitfalls in its diagnosis and management. Intraosseous lipoma is a rare benign tumor, mostly accounting for 0.1% of all bone tumors. The disease is usually asymptomatic and mainly involves the hips, vertebrae, ribs, and metaphysis of the long bones. However, the intraosseous lipoma of the skull is less common, especially with few cases having been reported to involve the sphenoid bone in the literature. We present a rare case of sphenoclival intraosseous lipoma in a 28-year-old female who presented with a history of chronic headache. A non-contrast computed tomography (NCCT) was ordered, which revealed a deviated nasal septum with thickening of bilateral ethmoidal sinuses with mastoiditis and a well-defined fat-containing intraosseous lesion in the clivus with a mean HU~ of -32 with few septations within. The risk of malignant transformation in intraosseous lipoma is very low. The differential diagnosis of intraosseous lipoma includes end stage of infection, infarct lesions, intraosseous meningioma, angiolipoma, and myxofibrous tumors.

Impact of patient and family engagement in improving continuous positive airway pressure adherence in patients with obstructive sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: The aim of the Improving CPAP Adherence Program was to assess the impact of a multidimensional treatment framework based on shared decision-making, patient activation, and caregiver engagement on improving long-term positive airway pressure (PAP) adherence in patients newly diagnosed with obstructive sleep apnea. METHODS: In this pilot study, patients aged ≥ 18 years with a new obstructive sleep apnea diagnosis who qualified for PAP treatment and lived with a caregiver were randomly assigned to receive either the multidimensional treatment (intervention, n = 28) or unrelated education (control group, n = 32). All patients and their caregiver participated in a group visit. The intervention group attended 4 structured sessions: interactive education, peer coaching, hands-on experience, and a semistructured motivational interview. The control group was educated on physical activity and lifestyle only. Objective PAP adherence data were obtained at baseline (day that they received PAP machine to group visit), group visit to 3 months, and 3-6 months. RESULTS: In an age-adjusted model, the mean daily use of PAP increased significantly over the 3 time periods (P = .03). Intervention-arm participants gained a mean 1.23 hours (95% confidence interval, 0.33-2.13) in PAP mean daily use between 3 and 6 months vs those in the control arm (P = .008). We saw no difference in the percentage of PAP adherence across time between the 2 arms. CONCLUSIONS: A multifaceted patient-centered intervention with caregiver engagement improved PAP adherence vs control levels, a beneficial effect sustained for the 6 months. Our findings suggest that caregivers, with the appropriate training, can improve patients' PAP adherence by providing a socially supportive environment. CITATION: Khan NNS, Todem D, Bottu S, Badr MS, Olomu A. Impact of patient and family engagement in improving continuous positive airway pressure adherence in patients with obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med. 2022;18(1):181-191.

Small Lymphocytic Lymphoma Presenting as a Breast Lump: A Rare Presentation of Non-Hodgkin's Lymphoma.

Approximately one-fourth of non-Hodgkin's lymphomas (NHLs) present with an extranodal origin. Primary and secondary involvements of the breast by lymphoma are rare because of the paucity of lymphoid tissue in the breast. Primary breast small lymphocytic lymphoma (SLL) typically presents as a manifestation of widespread chronic lymphocytic leukemia (CLL). A 58-year-old female presented to our clinic with a palpable breast mass. She had no cytopenias and her absolute peripheral B lymphocyte count was less than 5000/microL. The mass was biopsied and histology with immunohistochemistry showed neoplastic cells positive for CD23 and CD5 confirming the diagnosis of small B cell lymphocytic lymphoma of the breast. Further imaging revealed extensive mediastinal and retroperitoneal lymphadenopathy. Histopathology of bone marrow biopsy revealed diffuse infiltration with SLL. The patient was treated with six cycles of fludarabine, cyclophosphamide and rituximab (FCR) with excellent clinical response. To our knowledge, this is the first case of SLL infiltration of the breast without CLL treated successfully with FCR.

Radiation Recall Dermatitis following Radioactive Iodine Therapy: A New Observation.

A 47-year-old female, who had previously received adjuvant right breast radiation for ductal carcinoma in situ, presented with right breast edema, erythema, and pain. This developed about two and a half weeks following radioactive iodine therapy for thyroid carcinoma. A biopsy was performed to rule out malignancy, since inflammatory breast cancer can present with similar symptoms. This confirmed radiation recall dermatitis (RRD) as the most likely diagnosis. RRD is an inflammatory reaction occurring in a previously irradiated field and was first described in 1959. Subsequent reports in the literature have associated it with the administration of other drugs, mostly chemotherapy. To our knowledge, this is the first reported case of RRD following radioactive iodine therapy.

ANCA vasculitis: A manifestation of Post-Covid-19 Syndrome.

The SARS-CoV-2 infection has been found to present with different degrees of response and variable levels of inflammation. Patients who have recovered from the initial infection can develop long-term symptomatology. We present a unique case of a middle aged-healthy man who developed complications of ANCA-associated vasculitis after recovering from a mild COVID-19 infection. A previously healthy 53-year-old male presented with hemoptysis and acute renal failure. One month prior, the patient tested positive for COVID-19; not requiring hospitalization. Physical exam findings included bilateral lower extremity petechiae. CT Chest showed bilateral diffuse patchy lung consolidations with cavitary lesions with urinalysis revealing erythrocytes, +1 protein. Hemodialysis and workup for pulmonary-renal syndromes were initiated. Infectious workup results included: negative COVID-19, negative MTB-PCR, respiratory culture revealing yeast. Additional workup revealed; elevated CRP, D-Dimer, and Fibrinogen. Notably, the patient had; decreased C3 and C4 levels; negative Anti-GBM antibody; negative Anti-streptolysin-O; and positive ANCA assay, Proteinase antibody, and mildly positive Myeloperoxidase antibody. Worsening coagulopathy and atrophic kidneys delayed renal biopsy for definitive diagnosis. The patient's respiratory status acutely worsened during hemodialysis with imaging showing markedly increased pulmonary infiltrates. Upon urgent intubation, active frank red bleeding was noted, and the patient sustained 2 cardiac arrests with eventual expiration. Much is to be learned from the Novel SARS-CoV-2 virus and suspected complications. This case highlights a unique complication of COVID-19 leading to a possible AAV and the importance of keeping a broad differential when treating patients who have recovered from the initial infection.

Comparison of Different Molecular Subtypes with 14% Ki-67 Cut-off Threshold in Breast Cancer Patients of Pakistan- An Indication of Poor Prognosis.

BACKGROUND: Ki-67 is a proliferation marker that is used not only to categorize patients in luminal A and B subtypes of breast cancers, but also to determine the aggressiveness of the disease in triple negative and human epidermal growth factor 2 (HER2) over expressed molecular subtypes. The present study was designed to evaluate the role of Ki-67 with cut off value of 14% in molecular subgroups and its association with patient prognosis. METHODS: Immunostaining was performed on histopathologically confirmed sections (n = 278) to assess expression of Ki-67, estrogen receptor (ER), progesterone receptor (PR) and HER2. Immunoreactivity of molecules was recorded as percentage scoring. RESULTS: Adopting a cut off value of 14%, Ki-67 was high in 88%of the cases included in the study. High Ki-67 was significantly associated with pathological parameters including histological grade, advanced stage and nodal/distant metastasis. Immunoexpression of ER, PR and HER2 also showed strong correlation with high expression of Ki-67. Based on the St. Gallen classification, the cases were categorized into luminal A (10%) and luminal B (51%), triple negative (20%) and HER2 enriched (18%). Ki-67 index was also significantly high in 98% of HER2 enriched and 95% of TNBC patients. Interestingly, Ki-67 score with cut off value of 14% proved to be significant in deciphering prognosis in luminal patients. Moreover, high expression of Ki-67 also proved to be a marker of poor prognosis, especially in triple negative patients. CONCLUSION: We suggest that utilization of IHC4 status i.e. ER, PR, HER2 and Ki-67 along with pathological findings and molecular subtyping can considerably affect clinical as well as therapeutic decisions.

A rare case report of malignant peripheral nerve sheath tumor involving both the small bowel and large bowel.

Malignant peripheral nerve sheath tumor (MPNST) contains properties and histologic markers of both neural crest cells and mesenchymal cells. It is a rare diagnosis, with an incidence of 1:100,000/year or 4%-10% of soft-tissue sarcomas. There are very few cases reported and studied. Therefore, establishing a proper diagnosis and treatment of MPNST provides a challenge. We present this unique and rare case of metastatic MPNST of the small and large bowel with bone, pulmonary, liver, and splenic metastases. The patient subsequently developed hemorrhagic brain metastases and died 6 months after THE initial diagnosis.

Résumé La tumeur maligne de la gaine nerveuse périphérique (MPNST) contient des propriétés et des marqueurs histologiques des cellules de la crête neurale et du mésenchyme cellules. Il s'agit d'un diagnostic rare, avec une incidence de 1: 100 000 / an ou 4 à 10% des sarcomes des tissus mous. Il y a très peu de cas signalés et étudié. Par conséquent, l'établissement d'un diagnostic et d'un traitement appropriés de la MPNST constitue un défi. Nous présentons ce cas unique et rare de MPNST métastatique du petit et du gros intestin avec métastases osseuses, pulmonaires, hépatiques et spléniques. Le patient a ensuite développé métastases cérébrales hémorragiques et est décédé 6 mois après LE diagnostic initial.

Bilateral Renal Lymphangiectasia Associated With Polycythemia: A Rare Case Report.

Renal lymphangiectasia is a rare benign mesenchymal tumor of unclear etiology resulting from dilatation of perinephric lymphatic channels and formation of cystic masses. Polycythemia is a rarely associated finding with only five cases reported in the literature. We report a case of bilateral renal lymphangiectasia associated with polycythemia in a 38-year-old man who was managed conservatively with pain control. There are no clear guidelines for the management of renal lymphangiectasia; although most patients can be treated conservatively, some cases, whose diagnosis is unclear or develop complications, require definitive surgical excision.

An overview of the Novel Coronavirus (SARS-CoV-2) crisis in Fiji: Correspondence.

Fiji is facing the second wave of COVID-19 and has been recording increased number of COVID-19 cases. The response of Fijian Government is mainly directed towards obtaining international assistance in terms of expertise and vaccinations. While international support is necessary for the country, the Fijian Government also needs to consider the basic needs of the affected Fijians. In response, this article will provide an overview of the current COVID-19 crisis in Fiji to justify the need for reshaping the current approach of the Fijian Government.

Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy.

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of -27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

Von Hippel-Lindau Disease: A Rare Radiological Case Report of a Symptomatic Patient and His Asymptomatic Genetic Counterpart.

Von Hippel-Lindau (VHL) disease is an inherited syndrome manifested as a benign and malignant tumor. It is an autosomal dominant syndrome diagnosed approximately in 1 in 36,000 people. We report a case where male siblings presented with the involvement of bilateral kidneys and the multi-cystic lesion on the pancreas in both. Reverse transcription polymerase chain reaction (RT-PCR) was conducted to detect the VHL gene, which turned out to be a significant finding in our study. The rare involvement of both pancreas and kidneys was noted in the siblings with VHL in the present study. In patients with VHL-associated tumour presentations, the most frequent detection of pathogenic variants in the VHL gene is the result of directed genetic testing or inherited cancer gene panels. The presence of renal and pancreatic involvement is rare but a significant finding present within the family member who needs to be screened.