Pulmonary Alveolar Microlithiasis in a Middle-Aged Man Presenting With Respiratory Failure: A Case Report and Review of the Literature.

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease of the lung, characterized by diffuse deposits of intra-alveolar calcium phosphate microliths. It usually affects both sexes, presenting mostly in the second and third decades. The clinical course is highly variable, ranging from being asymptomatic to respiratory failure. PAM is usually diagnosed after careful clinical, radiological, and pathological evaluation, usually when patients present for other medical purposes. Here, a case of PAM in a middle-aged man presenting with acute-on-chronic hypoxemic respiratory failure is reported, with a review of the literature.

Formation of a Controllable Diffusion Barrier Layer on the Surface of Polydimethylsiloxane Films by Infrared Laser Irradiation.

Developing a diffusion barrier layer on material interfaces has potential applications in various fields such as in packaging materials, pharmaceuticals, chemical filtration, microelectronics, and medical devices. Although numerous physical and chemical methods have been proposed to generate the diffusion barrier layer, the complexity of fabrication techniques and the high manufacturing costs limit their practical utility. Here, we propose an innovative approach to fabricate the diffusion barrier layer by irradiating poly(dimethylsiloxane) (PDMS) with a mid-infrared (λ = 10.6 µm) CO2 laser. This process directly creates a diffusion barrier layer on the PDMS surface by forming a heavily cross-linked network in the polymer matrix. The optimal irradiation conditions were investigated by modulating the defocusing distance, laser power, and number of scanning passes. The barrier thickness can reach up to 70 µm as observed by the scanning electron microscope (SEM). The attenuated total reflectance (ATR), electron dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS) analyses collectively confirmed the formation of the SiOx structure on the modified surface based on the decreased methyl group signal and the increased oxygen/silicon ratio. The diffusion test with the model drugs (rhodamine B and donepezil) demonstrated that the modified surface exhibits effective diffusion barrier properties and the rate of drug diffusion through the modified barrier layer can be controlled by the optimization of the irradiation parameters. This novel approach provides the possibility to develop a controllable diffusion barrier layer in a biocompatible polymer with prospective applications in the fields of pharmaceuticals, packing materials, and medical devices.

A Rare Case of Disseminated Histoplasmosis With Hemophagocytic Lymphohistiocytosis Mimicking a Flare of Systemic Lupus Erythematosus in a Middle-Aged Man: A Case Report.

Disseminated histoplasmosis is a progressive granulomatous disease caused by Histoplasma capsulatum, which is an intracellular dimorphic fungus endemic to the Ohio and Mississippi River valleys in the United States. It is usually thought to be due to the failure of the activation of the T-cell-mediated immune response. Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal condition, in which histiocytes and lymphocytes build up in and damage organs and other blood cells. We present a 37-year-old man with a past medical history of systemic lupus erythematosus (SLE) complicated by lupus nephritis on immunosuppressive therapy who presented to the emergency department with hypotension and was admitted for acute kidney injury. Prior to the presentation, he had persistent fever, myalgias, cough, mild shortness of breath, and back pain. Computed tomography (CT) chest shows "eggshell" calcification; microbiology evaluation of peripheral blood smear revealed intracellular organism, morphologically consistent with H. capsulatum; and urine histoplasmosis antigen test confirmed the diagnosis of histoplasmosis. HLH diagnosis was made clinically after "clinical and testing criteria" were evaluated. Despite further management, he developed coagulopathy and sepsis, which led to his death. At autopsy, we found organomegaly of the liver, spleen, and kidneys. Microscopically, these enlarged organs show old fibrotic granulomas and granulomatous inflammation with suspected fungal organisms. Gomori's methenamine silver special stain confirmed these fungal organisms to be consistent with Histoplasma species (3-5 micron budding yeasts). This case highlights that physicians should be aware of the diagnostic challenge that disseminated histoplasmosis with HLH could pose in a patient with SLE, especially in patients on immunosuppression. Failure to recognize the infection promptly could lead to grievous complications and possibly death.

Concurrent Typhoid Fever and Dengue Hemorrhagic Fever: A Case Report.

Dengue virus can co-infect with a number of viruses, bacteria, and parasites of which dengue malaria co-infection is most well-known. We report a rare case of dengue virus co-infection with typhoid fever and the development of dengue hemorrhagic fever (DHF) during a dengue outbreak. The second spike of high-grade fever following initial defervescence with antibiotic therapy, hemorrhagic manifestations, new onset leucopenia and thrombocytopenia, and evidence of plasma leakage raised suspicion of DHF. Diagnosis of dengue co-infection was made by seroconversion for anti-dengue immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay (ELISA) on the seventh day of new-onset fever. Early recognition and judicious use of fluid therapy prevented the patient from developing shock and its complications. Prompt diagnosis, early recognition of plasma leakage, and appropriate management of DHF can reduce morbidity and mortality.

Effective utilization of magnetic nano-coupled cloned ß-xylanase in saccharification process.

The ß-xylanase gene (DCE06_04615) with 1041 bp cloned from Thermotoga naphthophila was expressed into E. coli BL21 DE3. The cloned ß-xylanase was covalently bound to iron oxide magnetic nanoparticles coated with silica utilizing carbodiimide. The size of the immobilized MNPs (50 nm) and their binding with ß-xylanase were characterized by Fourier-transform electron microscopy (FTIR) (a change in shift particularly from C-O to C-N) and transmission electron microscopy (TEM) (spherical in shape and 50 nm in diameter). The results showed that enzyme activity (4.5 ± 0.23 U per mL), thermo-stability (90 °C after 4 hours, residual activity of enzyme calculated as 29.89% ± 0.72), pH stability (91% ± 1.91 at pH 7), metal ion stability (57% ± 1.08 increase with Ca2+), reusability (13 times) and storage stability (96 days storage at 4 °C) of the immobilized ß-xylanase was effective and superior. The immobilized ß-xylanase exhibited maximal enzyme activity at pH 7 and 90 °C. Repeated enzyme assay and saccharification of pretreated rice straw showed that the MNP-enzyme complex exhibited 56% ± 0.76 and 11% ± 0.56 residual activity after 8 times and 13 times repeated usage. The MNP-enzyme complex showed 17.32% and 15.52% saccharification percentage after 1st and 8th time usage respectively. Immobilized ß-xylanase exhibited 96% residual activity on 96 days' storage at 4 °C that showed excellent stability.

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer.

Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N > 3000 combined), we performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mammalian target of rapamycin complex 1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and downregulated isoforms, respectively, in breast tumors compared with normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease-specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA-approved/investigational drugs. In summary, this work identifies novel cross talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.

Silibinin induces metabolic crisis in triple-negative breast cancer cells by modulating EGFR-MYC-TXNIP axis: potential therapeutic implications.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment modalities and poor prognosis. Metabolic reprogramming in cancer is considered a hallmark of therapeutic relevance. Here, we report disruption of metabolic reprogramming in TNBC cells by silibinin via modulation of EGFR-MYC-TXNIP signaling. Metabolic assays combined with LC-MS-based metabolomics revealed inhibition of glycolysis and other key biosynthetic pathways by silibinin, to induce metabolic catastrophe in TNBC cells. Silibinin-induced metabolic suppression resulted in decreased cell biomass, proliferation, and stem cell properties. Mechanistically, we identify EGFR-MYC-TXNIP as an important regulator of TNBC metabolism and mediator of inhibitory effects of silibinin. Highlighting the clinical relevance of our observations, the analysis of METABRIC dataset revealed deregulation of EGFR-MYC-TXNIP axis in TNBC and association of EGFRhigh -MYChigh -TXNIPlow signature with aggressive glycolytic metabolism and poor disease-specific and metastasis-free survival. Importantly, combination treatment of silibinin or 2-deoxyglucose (glycolysis inhibitor) with paclitaxel synergistically inhibited proliferation of TNBC cells. Together, our results highlight the importance of EGFR-MYC-TXNIP axis in regulating TNBC metabolism, demonstrate the anti-TNBC activity of silibinin, and argue in favor of targeting metabolic vulnerabilities of TNBC, at least in combination with mainstay chemotherapeutic drugs, to effectively treat TNBC patients.

COVID-19 Induced Acute Pancreatitis: A Case Report and Literature Review.

A 49-year-old female with no history of past medical illness presented to the emergency department with complaints of fever, dry cough, and shortness of breath. Initial evaluation revealed a temperature of 101°F, and on auscultation, the patient had scattered wheezing and rales in left lung fields. CT of the chest revealed pneumonic patches in the upper and lower segment of the left lung. Her COVID-19 testing came positive. On the second day of hospital admission, the patient experienced nausea, vomiting, and severe epigastric pain radiating to back. Laboratory analysis revealed a marked elevation of lipase and amylase. CT of the abdomen showed an edematous pancreas with diffuse enlargement. She was diagnosed with acute pancreatitis due to COVID-19 after carefully ruling out other causes. She was managed symptomatically, and improvement in her clinical condition was observed and was discharged with outpatient follow-up. Although acute pancreatitis is rare in patients with COVID-19, it should be considered as a differential diagnosis in patients with severe epigastric pain and respiratory symptoms.

Lyme Disease and Severe Hyperbilirubinemia: A Rare Presentation of Lyme Disease.

A 39-year-old-man presented to the emergency room with a complaint of febrile jaundice and diffuse arthralgia. The patient had a temperature of 100°F, severe jaundice, and scleral icterus. Laboratory workup showed severe hyperbilirubinemia and elevated serum creatinine, and the rest of the serum chemistry was unremarkable. The ultrasound and computed tomography (CT) of the abdomen was normal. The patient had a recent history of travel to an endemic area for Lyme disease. After an extensive workup, all other possible etiologies had been ruled out, and the patient was started on empirical doxycycline by considering the patient's recent history of travel. Serum serologic test confirmed Lyme disease. His bilirubin and creatinine improved gradually. His fever subsided in three days, and he was discharged with outpatient follow-up. Although hyperbilirubinemia is rare in Lyme disease, it should be considered as a differential diagnosis in patients with severe jaundice and a recent history of travel.

Constipation in Pediatric Patients with Lower Urinary Tract Symptoms.

OBJECTIVE: To determine the frequency of constipation in patients with pediatric age group presenting with Lower Urinary Tract Symptoms (LUTS). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Outpatient Department of Urology in Pakistan Kidney Institute at Shifa International Hospital, Islamabad, from November 2012 to February 2014. METHODOLOGY: Two hundred pediatric patients presenting with Lower Urinary Tract Symptoms (LUTS) were studied in terms of age, gender, obstructive and irritative types of LUTS along with any associated symptoms. Constipation was assessed by Bristol stool chart in these patients. Patients with exstrophy of bladder were excluded from the study. Descriptive statistics were measured for both qualitative and quantitative variables. For qualitative variables like gender, presenting symptoms, constipation and stool types, percentages and frequencies were calculated. For quantitative variables like age, percentages / mean ±SD were calculated. RESULTS: Mean age was 6.87 ±3.64 years with a range of 2 - 14 years. Constipation was found in 37.5% of the pediatric patients with lower urinary tract symptoms. CONCLUSION: Constipation is frequent and overlooked problem in pediatric patients having urinary symptoms. Irritative lower urinary tract symptoms are more common. Children up to 5 years of age are the most common sufferers. Knowing the burden of constipation in such patients can help physicians in better treatment of such cases.

EFFICACY OF ENDOSCOPIC TREATMENT FOR PRIMARY VESICOURETERIC REFLUX IN CHILDREN.

BACKGROUND: Vesicoureteral reflux (VUR) is a common anomaly affecting 1-3% of all children and 30-50% of those with urinary tract infection (UTI). In the past febrile vesicoureteric reflux on chronic antibiotic prophylaxis were treated by open surgery. Now a day's endoscopic injection of a bulking material has replaced open surgical procedure in cases of primary VUR. Our objective was to assess the efficacy of endoscopic treatment for primary vesico-ureteric reflux in children. METHODS: This was a descriptive case series. One hundred and five patients with either unilateral or bilateral VUR (181 ureters) underwent endoscopic treatment for primary VUR between January 2011 and January 2014. Children from 1 to 12 years of age with grade-II to IV reflux on preoperative voiding cystourethrogram (VCUG) were enrolled through consecutive non-probability sampling. Efficacy of treatment was evaluated at three months post injection by a standard VCUG. Ureters with no or grade-I reflux were considered successful treatment. RESULTS: Out of 105 patients 76 had bilateral while 29 had unilateral reflux. Mean age was 5.7 years (SD ± .7). Among 181 refluxing ureters, 116 (64%) were free of reflux, while 49 (27%) showed down gradation and 16 (8.8%) showed no response to treatment on postoperative VCUG. CONCLUSION: Endoscopic treatment for VUR is a viable option for patients with primary VUR and may be considered in management of such cases.

Purification and characterization of cloned alkaline protease gene of Geobacillus stearothermophilus.

Thermostable alkaline serine protease gene of Geobacillus stearothermophilus B-1172 was cloned and expressed in Escherichia coli BL21 (DE3) using pET-22b(+), as an expression vector. The growth conditions were optimized for maximal production of the protease using variable fermentation parameters, i.e., pH, temperature, and addition of an inducer. Protease, thus produced, was purified by ammonium sulfate precipitation followed by ion exchange chromatography with 13.7-fold purification, with specific activity of 97.5 U mg(-1) , and a recovery of 23.6%. Molecular weight of the purified protease, 39 kDa, was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme was stable at 90 °C at pH 9. The enzyme activity was steady in the presence of EDTA indicating that the protease was not a metalloprotease. No significant change in the activity of protease after addition of various metal ions further strengthened this fact. However, an addition of 1% Triton X-100 or SDS surfactants constrained the enzyme specific activity to 34 and 19%, respectively. Among organic solvents, an addition of 1-butanol (20%) augmented the enzyme activity by 29% of the original activity. With casein as a substrate, the enzyme activity under optimized conditions was found to be 73.8 U mg(-1) . The effect of protease expression on the host cells growth was also studied and found to negatively affect E. coli cells to certain extent. Catalytic domains of serine proteases from eight important thermostable organisms were analyzed through WebLogo and found to be conserved in all serine protease sequences suggesting that protease of G. stearothermophilus could be beneficially used as a biocontrol agent and in many industries including detergent industry.