Decoding Complexity in Synthetic Oligonucleotides: Unraveling Coeluting Isobaric Impurity Ions by High Resolution Mass Spectrometry.

Analyzing coeluting impurities with similar masses in synthetic oligonucleotides by liquid chromatography-mass spectrometry (LC-MS) poses challenges due to inadequate separation in either dimension. Herein, we present a direct method employing fully resolved isotopic envelopes, enabled by high resolution mass spectrometry (HRMS), to identify and quantify isobaric impurity ions resulting from the deletion or addition of a uracil (U) or cytosine (C) nucleotide from or to the full-length sequence. These impurities may each encompass multiple sequence variants arising from various deletion or addition sites. The method utilizes a full or targeted MS analysis to measure accurate isotopic distributions that are chemical formula dependent but nucleotide sequence independent. This characteristic enables the quantification of isobaric impurity ions involving sequence variants, a capability typically unavailable in sequence-dependent MS/MS methods. Notably, this approach does not rely on standard curves to determine isobaric impurity compositions in test samples; instead, it utilizes the individual isotopic distributions measured for each impurity standard. Moreover, in cases where specific impurity standards are unavailable, the measured isotopic distributions can be adequately replaced with the theoretical distributions (calculated based on chemical formulas of standards) adjusted using experiment-specific correction factors. In summary, this streamlined approach overcomes the limitations of LC-MS analysis for coeluting isobaric impurity ions, offering a promising solution for the in-depth profiling of complex impurity mixtures in synthetic oligonucleotide therapeutics.

UV and Visible Light-Driven Production of Hydroxyl Radicals by Reduced Forms of N, F, and P Codoped Titanium Dioxide.

The photocatalytic activities of reduced titanium dioxide (TiO2) materials have been investigated by measuring their ability to produce hydroxyl radicals under UV and visible light irradiation. Degussa P25 TiO2 was doped with nitrogen (N), fluorine (F), and/or phosphorus (P) and then subjected to surface modification employing a thermo-physicochemical process in the presence of reducing agent sodium borohydride (NaBH4). The reduced TiO2 materials were characterized by a number of X-ray, spectroscopic and imaging methods. Surface doping of TiO2 was employed to modulate the band gap energies into the visible wavelength region for better overlap with the solar spectrum. Hydroxyl radical generation, central to TiO2 photocatalytic water purification applications, was quantitated using coumarin as a trap under UV and visible light irradiation of the reduced TiO2 materials. At 350 nm irradiation, the yield of hydroxyl radicals generated by the reduced forms of TiO2 was nearly 90% of hydroxyl radicals generated by the Degussa P25 TiO2. Hydroxyl radical generation by these reduced forms of TiO2 was also observed under visible light irradiation (419 and 450 nm). These results demonstrated that simple surface modification of doped TiO2 can lead to visible light activity, which is important for more economical solar-driven applications of TiO2 photocatalysis.

Acute pancreatitis associated with acute viral hepatitis A (HAV) - a case report.

In this case report, a young woman had acute viral hepatitis (HAV) and acute pancreatitis together. She was admitted to our hospital with fever, jaundice and abdominal pain. Hepatic and pancreatic enzymes were elevated. Her serum alanine aminotransferase (ALT) level was high. An initial abdominal ultrasound was per-formed at hospital and revealed features of acute viral hepatitis. Spiral computed imaging revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness. HAV infection was diagnosed by the detection of immunoglobulin M (IgM) against HAV in the serum. She was closely monitored and treated conservatively. On 10th day of hospital admission she was discharge after an uneventful recovery. In the current literature HAV infections have rarely been reported as a cause of acute pancreatitis.

Cutaneous metastatic adenocarcinoma - a case report.

Cutaneous metastases from carcinoma are relatively uncommon in clinical practice but they are very important to recognize. Cutaneous metastases may herald the diagnoses, can lead to accurate diagnoses and timely treatment. A high index of suspicion is required because the clinical finding may be subtle. The patient of cutaneous metastases may present with rapidly developing nodules or tumors. Although asymptomatic in most instances, Pain and tenderness may be noted. Here we described a 38 year old male who presented with fever, anorexia, weight loss and multiple painful nodules, plaques and tumors on his scalp, face, upper trunk and proximal portion of the upper limbs. This case present with cutaneous metastatic adenocarcinoma with atypical presentation and detection of cutaneous metastasis before primary tumor detection.

Budd-Chiari syndrome.

A 16 years old boy hailing from Comilla presented with sudden onset of upper abdominal pain, ascites and generalized muscle wasting for 3 months. Ultrasonogram (USG), Color Doppler and Venography was done and diagnosed him a case of Budd-Chiari syndrome. The patient was treated with salt and water restriction, diuretics, repeated palliative ascetic fluid aspiration with re-accumulation within 1-2 days. He was also given Low molecular weight Heparin for 7 days, overlapped and followed by warfarin 10mg/day with target INR 2.5-3.5. Consultation with hepatobiliary surgeon was done for shunt operation, but operation was not possible due to poor general condition. This patient improved satisfactorily with low molecular weight heparin, warfarin and supportive measures. Budd-Chiari syndrome is a rare veno-occlusive disorder involving hepatic vasculature.

Juvenile onset ankylosing spondylitis with ankylosing tarsitis: a rare combination.

Ankylosing spondylitis is the most common whereas ankylosing tarsitis is the least common subgroup of juvenile onset spondyloarthritides. In our recent study a male presented with ankle joint pain and swelling with limited movements and characteristic radiological changes including; periarticular swelling, thickened heel pad, hyperostosis and reduced ankle, calcaneo-cuboid and talo-navicular joint space for ankylosing tarsitis. He also had persistent inflammatory low back pain with radiological sacroilitis satisfying the clinical features for ankylosing spondylitis. The patient was treated with different anti-inflammatory agents including intra-articular methyl-prednisolone with short-term relief. Associated back pain was improved with spine mobilizing exercise.

Tandem mass spectrometric sequence characterization of synthetic thymidine-rich oligonucleotides.

Tandem mass spectrometry (MS/MS) can provide direct and accurate sequence characterization of synthetic oligonucleotide drugs, including modified oligonucleotides. Multiple factors can affect oligonucleotide MS/MS sequencing, including the intrinsic properties of oligonucleotides (i.e., nucleotide composition and structural modifications) and instrument parameters associated with the ion activation for fragmentation. In this study, MS/MS sequencing of a thymidine (T)-rich and phosphorothioate (PS)-modified DNA oligonucleotide was investigated using two fragmentation techniques: trap-type collision-induced dissociation ("CID") and beam-type CID also termed as higher-energy collisional dissociation ("HCD"), preceded by a hydrophilic interaction liquid chromatography (HILIC) separation. A low to moderate charge state (-4), which predominated under the optimized HILIC-MS conditions, was selected as the precursor ion for MS/MS analysis. Comparison of the two distinctive ion activation mechanisms on the same precursor demonstrated that HCD was superior to CID in promoting higher sequence coverage and analytical sensitivity in sequence elucidation of T-rich DNA oligonucleotides. Specifically, HCD provided more sequence-defining fragments with higher fragment intensities than CID. Furthermore, the direct comparison between unmodified and PS-modified DNA oligonucleotides demonstrated a loss of MS/MS fragmentation efficiency by PS modification in both CID and HCD approaches, and a resultant reduction in sequence coverage. The deficiency in PS DNA sequence coverage observed with single collision energy HCD, however, was partially recovered by applying HCD with multiple collision energies. Collectively, this work demonstrated that HCD is advantageous to MS/MS sequencing of T-rich PS-modified DNA oligonucleotides.

Evaluation of Marjoram Leaves (Oregano vulgar) as Feed Supplement on Quality of Semen in Awasian Pollination Rams.

This study aimed to evaluate the effect of Marjoram leaves (Oregano vulgar) as a feed supplement on sexual efficiency and semen quality in Awasian pollination rams. The study was conducted on ten rams in one of the private fields in the Babylon governorate. The rams were divided randomly into two groups. First group rams are regarded as a control group (group A) that feeds on exceptional concentric food for pollination rams. The second group consists of 5 rams (group B) provided with the same concentric food plus a supplement of 3 mg/kg of body weight of Oregano vulgar leaves (fresh) 3 times daily for 49 days before the pollination season (April and May). Semen samples were collected at the end of 49 days by artificial vagina to evaluate the volume of ejaculate, sperm number, concentration, motility, viability, and deformities, and to measure the sperm pleomorphic parameters of the head, nucleus, and acrosome. The antioxidant status of seminal plasma was evaluated by measuring superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC). ELISA tests were used on blood serum samples to measure the hormone levels of luteinizing hormone (LH), testosterone, and estrogen. The study demonstrated a significant increase in motility, the viability of sperm, and decreasing deformities. There was no significant variation in perimorphic parameters of the head, nucleus, and acrosome sperm after using the fresh leaves of Oregano vulgar as supplementation to Awasion sheep. However, there was an increase in the antioxidant enzymes (SOD, GPX, and TAC) in seminal plasma and an increase in LH, testosterone, and estrogen in the blood serum of experimental group B. These findings show that using fresh leaves of Oregano vulgar improved the sexual efficiency of pollinated rams and maintained the physiology and perimorphic parameters of semen and sperm.

The effect of tamoxifen on the lipid profile in women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The effect of tamoxifen administration on serum lipids in females remains unclear. The studies which have explored this topic have produced conflicting results, probably due to discrepancies in the length of the intervention, differences in baseline variables or other factors. To answer this research question, we decided to conduct this systematic review and meta-analysis to assess the effects of tamoxifen on the lipid profile in women. METHODS: A comprehensive search was conducted in Web of Science, Scopus, PubMed/Medline and Embase, from the inception of these databases up to June 2021. We used a random effects meta-analysis to generate the combined results. RESULTS: The overall findings were generated from 18 eligible trials. As compared to placebo, tamoxifen led to a notable reduction of the total cholesterol (TC) (WMD: -23.03 mg/dL, 95% CI: -25.94 to -20.12, P˂0.001), and the low-density lipoprotein-cholesterol (LDL-C) (WMD: -18.68 mg/dL, 95% CI: -24.31 to -13.04, P˂0.001). However, tamoxifen did not alter triglycerides (TG) concentrations (WMD: +1.06 mg/dL, 95% CI: -11.08 to 13.20, P = 0.864) significantly. A pronounced reduction of the high-density lipoprotein-cholesterol (HDLC) was noted in the RCTs with a duration of ≤52 weeks (WMD: -2.06 mg/dL) and when tamoxifen was administered in participants with a BMI ≥25 kg/m2 (WMD: -1.42 mg/dL). Notable reductions in TC (WMD: -23.57 mg/dL) and LDL-C (WMD: -19.21 mg/dL) was detected when the dose of tamoxifen was ≥20 mg/day. Moreover, a significant reduction of TC (WMD: -20.23 mg/dL) and LDL-C (WMD: -24.13 mg/dL) was observed in the RCTs with a duration of ≤52 weeks. CONCLUSION: Tamoxifen can alter the lipid profile in females, particularly by decreasing TC, LDL-C and HDLC. Tamoxifen can further reduce TC and LDL-C if the dose of administration is ≥20 mg/day, the treatment duration is ≤52 weeks and if it prescribed in subjects with dyslipidemia.

An efficient eco advanced oxidation process for phenol mineralization using a 2D/3D nanocomposite photocatalyst and visible light irradiations.

Nanocomposites (CNTi) with different mass ratios of carbon nitride (C3N4) and TiO2 nanoparticles were prepared hydrothermally. Different characterization techniques were used including X-ray diffraction (XRD), UV-Vis diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), transmission electron spectroscopy (TEM) and Brunauer-Emmett-Teller (BET). UV-Vis DRS demonstrated that the CNTi nanocomposites exhibited absorption in the visible light range. A sun light - simulated photoexcitation source was used to study the kinetics of phenol degradation and its intermediates in presence of the as-prepared nanocomposite photocatalysts. These results were compared with studies when TiO2 nanoparticles were used in the presence and absence of H2O2 and/or O3. The photodegradation of phenol was evaluated spectrophotometrically and using the total organic carbon (TOC) measurements. It was observed that the photocatalytic activity of the CNTi nanocomposites was significantly higher than that of TiO2 nanoparticles. Additionally, spectrophotometry and TOC analyses confirmed that degraded phenol was completely mineralized to CO2 and H2O with the use of CNTi nanocomposites, which was not the case for TiO2 where several intermediates were formed. Furthermore, when H2O2 and O3 were simultaneously present, the 0.1% g-C3N4/TiO2 nanocomposite showed the highest phenol degradation rate and the degradation percentage was greater than 91.4% within 30 min.

Helicobacter pylori infection in children in Saudi Arabia.

20 children with suspected Helicobacter pylori (H. pylori) infection are presented. The mean age of the children was 9.4 years (range 4-13 years). The mean H. pylori IgG and IgA antibodies were 677 units and 760.7 units respectively. Antral biopsy cultures were positive in five children. Histopathology of the gastric antral and duodenal biopsies showed H. pylori gastritis in 11 children, duodenitis and gastritis in five, normal histology in three and one child had normal histology with H. pylori like organism on the surface of the antral mucosa. From this study, we conclude that serology is a good diagnostic test for H. pylori infection in Saudi Arabia.

Comparison of Helicobacter pylori antibody levels in children in Riyadh.

Helicobacter pylori (H. pylori) antibodies were determined in 229 asymptomatic children and 43 symptomatic children in Saudi Arabia. There is a significant difference in IgG and IgA antibodies for both asymptomatic and symptomatic children (p = 0.00001). We conclude that Helicobacter pylori antibody determination by ELISA is a good screening test for diagnosis of Helicobacter pylori infection in children in Saudi Arabia.

Pattern of gastroesophageal reflux in children.

OBJECTIVE: Gastroesophageal reflux disease is a common health problem in children worldwide. There are no published data on this disease in children from Saudi Arabia. The objective of this study is, therefore, to report on the pattern of gastroesophageal reflux disease in Saudi children. METHODS: Retrospective review of all children referred to the Pediatric Gastroenterology Division at King Khaled University Hospital in Riyadh. RESULTS: The diagnosis was confirmed in 85 children, all but 2 were Saudi nationals, and the male to female ratio was 1.6. The median age of onset of symptoms was 10 months, whereas the median age at referral was 20 months. The pattern of clinical presentation indicates that vomiting is the most common presentation occurring in 82% of the children, followed by respiratory disease in 38%. An underlying condition was found in 41% of the children, (35/85) the most common of which was neurological impairment. Peptic esophagitis was present in 51.5% of the children who underwent endoscopy. The median duration of follow up was 6 months. Good response to medical therapy was documented in 72% of normal children and 27% of those with underlying disease. All of the 23 children who had fundoplication in our institution had one or more of the underlying disorders. CONCLUSION: Gastroesophageal reflux disease is a common problem in Saudi children. The overall pattern in this report is similar to descriptions in the literature. Prospective multicenter studies are needed to confirm this pattern and to provide more focused descriptions of other aspects of the disease.

Performances of toluene removal by activated carbon derived from durian shell.

In the effort to find alternative low cost adsorbent for volatile organic vapors has prompted this research in assessing the effectiveness of activated carbon produced from durian shell in removing toluene vapors. Durian shells were impregnated with different concentrations of H3PO4 followed by carbonization at 500 °C for 20 min under nitrogen atmosphere. The prepared durian shell activated carbon (DSAC) was characterized for its physical and chemical properties. The removal efficiency of toluene by DSAC was performed using different toluene concentrations. Results showed that the highest BET surface area of the produced DSAC was 1404 m2/g. Highest removal efficiency of toluene vapors was achieved by using DSAC impregnated with 30% of acid concentration heated at 500 °C for 20 min heating duration. However, there is insignificant difference between removal efficiency of toluene by DSAC and different toluene concentrations. The toluene adsorption by DSAC was better fitted into Freundlich model.

Conjugated hyperbilibubinaemia in infancy (infantile cholestasis).

The finding of high conjugated bilirubin needs prompt evaluation to rule out liver or bile duct pathology. If assessment of total and direct bilirubin is carried routinely in any infant whose jaundice persists for more than 2 weeks, early identification of a group of children who need corrective surgery for atresia of the extra hepatic bile duct is possible. The aim of this review is to look at common causes of infantile cholestasis with emphasis on evaluation, diagnosis, complications, treatment and outcome of infant with neonatal cholestasis.

Aetiology of chronic diarrhoea in children: experience at King Khalid University Hospital, Riyadh, Saudi Arabia.

Forty-eight cases of chronic diarrhoea in children seen at King Khalid University Hospital over a 5-year period were analysed. The mean age at presentation was 1.8 years (range 0.08-10 years); 34 were boys and 14 girls. Forty-four patients were Saudi and four were non-Saudi Arabs. Most children presented with failure to thrive and pallor. The aetiological factors identified were: the post-gastro-enteritis syndrome with or without lactose intolerance in 16 (33%); coeliac disease in ten (21%); congenital chloride diarrhoea in five (10%); glucose-galactose malabsorption and acrodermatitis enteropathica, each in three (6%); ulcerative colitis, intestinal lymphangiectasia, cow's milk protein intolerance and ataxia telangiectasia, each in two (4%); and giardiasis, immune deficiency and cystic fibrosis, each in one (2%). Five children died.

Clinical presentation and management of acute gastro-enteritis in in-patient children at King Khalid University Hospital, Riyadh, Saudi Arabia.

In a retrospective survey, case notes of all children with acute gastro-enteritis (AGE) admitted to our hospital between 1984 and 1988 were reviewed. The total number of cases was 300. The mean age was 14 months (range 1-60 mths): 67% of cases were boys and 33% girls. Eleven per cent were exclusively breastfed. The clinical presentation was diarrhoea and vomiting in 81%, diarrhoea alone in 15%, and vomiting primarily in 4%. All children had good nutritional status, i.e. both their height and weight were between the 5th and 90th percentile for their age and none showed signs of marasmus or kwashiorkor. Forty-six per cent of the children had AGE without dehydration. Mild, moderate and severe dehydration was present in 41%, 10% and 3% of cases, respectively. Isotonic, hypotonic and hypernatraemic dehydration was present in 95%, 3% and 2% of cases of dehydration, respectively. Sixty-five per cent of cases were given intravenous (IV) fluids. The mean duration of IV administration was 1 day, with a range of 1-7 days. Twenty-two per cent of the children were given oral rehydration solution (ORS) initially, and 13% were given IV plus ORS. None of the children died of gastro-enteritis. It is concluded that there was excessive use of IV fluids, and that there is an urgent need to encourage the use of ORS.