Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions.

For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.

Calibration of Ring Oscillator-Based Integrated Temperature Sensors for Power Management Systems.

This paper details the development and validation of a temperature sensing methodology using an un-trimmed oscillator-based integrated sensor implemented in the 0.18-µm SOI XFAB process, with a focus on thermal monitoring in system-on-chip (SoC) based DC-DC converters. Our study identifies a quadratic relationship between the oscillator output frequency and temperature, which forms the basis of our proposed calibration mechanism. This mechanism aims at mitigating process variation effects, enabling accurate temperature-to-frequency mapping. Our research proposes and characterizes several trimming-free calibration techniques, covering a spectrum from zero to thirty-one frequency-temperature measurement points. Notably, the Corrected One-Point calibration method, requiring only a single ambient temperature measurement, emerges as a practical solution that removes the need for a temperature chamber. This method, after adjustment, successfully reduces the maximum error to within ±2.95 °C. Additionally, the Two-Point calibration method demonstrates improved precision with a maximum positive error of +1.56 °C at -15 °C and a maximum negative error of -3.13 °C at +10 °C (R2 value of 0.9958). The Three-Point calibration method performed similarly, yielding an R2 value of 0.9956. The findings of this study indicate that competitive results in temperature sensor calibration can be achieved without circuit trimming, offering a viable alternative or a complementary approach to traditional trimming techniques.

A Copper-Catalyzed Interrupted Domino Reaction for the Synthesis of Fused Triazolyl Benzothiadiazine-1-oxides.

Copper(I)-catalyzed domino reactions of 2-azido sulfoximines with 1-iodoalkynes yield fused triazolyl-containing benzothiadiazine-1-oxides. The protocol features the synthesis of two fused heterocyclic rings in one step with good to excellent yields and a broad functional group tolerance. Detailed mechanistic investigations indicate that a copper π-complex initiates a cycloaddition and oxidative C-N coupling reaction sequence. The results suggest an interrupted domino process involving an iodinated triazole as a key intermediate.

Electro-mechanochemical approach towards the chloro sulfoximidations of allenes under solvent-free conditions in a ball mill.

An electro-mechanochemical protocol for the synthesis of vinylic sulfoximines has been developed. Utilising mechanochemically strained BaTiO3 nanoparticles, the catalytic active system is generated in situ by the reduction of copper(II) chloride. Various combinations of electron-donating and -withdrawing groups are tolerated, and the approach leads to products with difunctionalised double bonds in good to excellent yields. Attempts to add a sulfoximidoyl chloride to an alkyne proved difficult. Additions of a sulfonyl iodide to allenes and alkynes proceeded smoothly in the presence of silica gel without the need for activation by a piezoelectric material.

Emotional Contagion Scale and Mental Health Status during the First Wave of COVID-19 Pandemic, National Assessment.

Background: This great pandemic of COVID-19 has been a unique stressor that affected all communities in 2020. This study aims to examine the prevalence of anxiety and depression due to the COVID-19 pandemic in Saudi Arabia and to study the emotional cognition scale in the Kingdom of Saudi Arabia (KSA) in relation to the COVID-19 pandemic. Methodology: A descriptive cross-sectional study was conducted on 857 inhabitants randomly selected from the 13 administrative regions of Saudi Arabia, using a validated self-administrated questionnaire comprising six sections. The collected data were summarized and analyzed. Results: Among the majority of the studied participants, 377 (44.0%) were aged from 35 to less than 50 y. There were 489 (57.1%) females and 368 (42.9%) males, 616 (71.9%) Saudi nationals, 715 (83.4%) university-educated or postgraduate, 619 (72.2%) unmarried and 238 (27.8%) married, and 663 (77.4%) living in areas under partial lockdown. The resultant elevated total depression score was statistically significant (p<0.05) for the following: participants younger than 35y, females, Saudis, those with lower education levels, those who were married, students, those with work suspension during the COVID-19 pandemic, and amongst those who experienced complete lockdown. Among the majority of the studied participants, 355 (41.2%) showed mild depression, and 281(32.6) showed moderate anxiety, and were in the growth zone. In addition, the elevated total anxiety score was statistically significant (p<0.05) amongst the following; younger participants, females, Saudi nationals, those with lower educational levels, those who were unmarried, students, those with telework, and those with no curfew. Conclusion: The adverse mental health effects were more prevalent among particular groups of the population, such as females, adults under 35 years old, students, those with lower educational attainments, and those suffering from chronic illnesses. Anxiety was significantly correlated with depression. The practice of preventive measures, e.g., wearing masks, and social distancing to prevent the spread of COVID-19, may have had psychological benefits during the pandemic. Summary: We assessed the mental health status in Saudi Arabia during the first wave of the COVID-19 pandemic. Mild depression and moderate anxiety were prevalent problems, with many determinants and interrelations. Fear was the most infectious emotion, while happiness was the highest.

Delta QRS distinguishes Ito -mediated J waves from pseudo J waves produced by conduction delay on body surface electrocardiographic.

BACKGROUND: On surface electrocardiographic (ECGs), it is difficult to differentiate Ito -mediated J waves, a repolarization phenomenon seen in J wave syndromes (JWS) from terminal QRS deflections that mimic J waves (pseudo J waves) in intraventricular conduction delay (IVCD), an abnormality in depolarization. We hypothesize that the difference between the "maximum QRS duration" inclusive of J point or terminal QRS deflections and the minimum QRS duration identified across a 12-lead ECG is significantly larger in Ito -mediated J waves, and can serve as a marker to make this distinction. METHODS: A retrospective analysis was performed on adults with ECGs consisting of one of the four following manifestations: J waves associated with hypothermia and early repolarization, and pseudo J waves associated with right bundle branch block (RBBB) and non-specific intraventricular conduction delay (NS-IVCD). All ECGs were assessed individually and the maximum and minimum discrete QRS deflections on 12-lead tracings, defined as "QRSmax " and QRSmin , were identified. The difference between "QRSmax " and QRSmin , designated as ∆QRS, was calculated and compared across the studied populations. RESULTS: A total of 60 patients consisting of 15 patients in each arm were included in the study. ΔQRS was significantly larger in the hypothermia and early repolarization groups, compared to RBBB and NS-IVCD (p < .0001), with the following mean ∆QRS: hypothermia 54.3 ± 13.7 ms, early repolarization pattern 47.3 ± 15.3 ms, RBBB 19.3 ± 6.5 ms, and NS-IVCD 16.0 ± 6.6 ms. CONCLUSION: ∆QRS may serve as a reliable ECG parameter for distinguishing Ito -mediated J waves from pseudo J waves produced by delayed intraventricular conduction.

Synthesis, DFT calculation, pharmacological evaluation, and catalytic application in the synthesis of diverse pyrano[2,3-c]pyrazole derivatives.

Pyranopyrazole and its derivatives are classified to be a pharmacologically significant active scaffold for almost all modes of biological activities. In this work, An efficient, green, and facile three-component reaction for preparing pyrano[2,3-c]pyrazole derivatives via the condensation reaction of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, ethyl acetoacetate, and malononitrile in the presence of ZnO Nanoparticle. The products are produced with high yields and in shorter reaction times. It also is mild, safe, green, and environmentally friendly. The geometric parameters such as dipole moment, bond length, dihedral angles, total energy, heat of formation, atomic charges and energies at a highly accurate for prepared compounds were computed by Denisty Functional Theory along with the B3LYP functional. The newly synthesized compounds were screened for their anti-inflammatory and antioxidant activity. Some of the tested compounds displayed promising activities. The newly prepared compounds were found to be potent towards the antioxidant activity. Results indicated that compounds 11 and 12 exhibited significant (p ≥ 0.05) in vitro total antioxidant activity as 44.93 ± 0.15 and 39.60 ± 0.10 U/ML, respectively higher than standard ascorbic acid (29.40 ± 0.62).

Amino Acid-Derived trans- N-Chloroformylimidazolidinones: Scalable, Stereoselective Synthesis, Structure, and Utility.

N-acyl imidazolidinones, which are key intermediates in the stereoselective synthesis of amino acids by "self-regeneration of stereochemistry" methods, are classically made by only moderately diastereoselective methods. We now report that cyclization of pivaldimino-amides with phosgene in the presence of pyridine may be made fully diastereoselective for the trans-N-chloroformylimidazolidinones, and we detail the conformational features of the products. We show that despite the presence of the electrophilic carbamoyl chloride function the products show remarkable stability and may be deprotonated to form enolates with useful reactivity for the synthesis of amino acid derivatives.

Asymmetric and Geometry-Selective α-Alkenylation of α-Amino Acids.

Both E- and Z-N'-alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α-amino acids. Generation of their enolate derivatives in the presence of K+ and [18]crown-6 induces intramolecular migration of the alkenyl group from N' to Cα with retention of double bond geometry. DFT calculations indicate a partially concerted substitution mechanism. Hydrolysis of the enantiopure products under acid conditions reveals quaternary α-alkenyl amino acids with stereodivergent control of both absolute configuration and double bond geometry.

Evidence-based pharmaceutical care: The next chapter in pharmacy practice.

INTRODUCTION: Pharmacy is a very dynamic profession and the role of the pharmacist is improving with the expansion of the scope of services and the introduction of new subspecialties over time. Moving from being medication dispensers to outcome-oriented and patient-focused care providers; pharmacists will carry more responsibility and commitment to improve their knowledge and practice. Being updated and evidence-based is a key tool to achieve effective pharmaceutical care services. The primary purpose of this article is to highlight the concept of "evidence based pharmaceutical care" as professional practice to improve the quality of pharmaceutical care. METHODS: Literature for relevant evidence was searched by Medline (through PubMed), Cochrane library using the keywords: pharmaceutical care, evidence-based and pharmacy practice. Also a manual search through major journals for articles referenced in those located through PubMed was done. RESULTS AND DISCUSSION: There is strong data showing that pharmaceutical care lead to improvement in health outcomes and cost-effective therapy. More efforts, policies and qualified staff are needed to establish the "evidence-based pharmaceutical care" as new daily professional practice. Evidence to support pharmacists in their emerging role as care providers is available to improve the efficacy and quality of pharmaceutical care. Education and specialized training practicing evidence based approach are vital to prepare pharmacists to provide high quality pharmaceutical care. CONCLUSION: As care providers, pharmacists are effective in providing high quality patient care and being members in multidisciplinary clinical teams is needed to give them the opportunity. Evidence based pharmaceutical care is a natural and logical emerging concept in the modern pharmacy practice to achieve high quality and more effective pharmaceutical care but still more efforts and resources are needed to promote new attitude toward more professional career.