Cross-coupling reactions towards the synthesis of natural products.

Cross-coupling reactions are powerful synthetic tools for the formation of remarkable building blocks of many naturally occurring molecules, polymers and biologically active compounds. These reactions have brought potent transformations in chemical and pharmaceutical disciplines. In this review, we have focused on the use of cross-coupling reactions such as Suzuki, Negishi, Heck, Sonogashira and Stille in the total synthesis of some natural products of recent years (2016-2020). A short introduction of mentioned cross-coupling reactions along with highlighted aspects of natural products has been stated in separate sections. Additionally, few examples of natural products via incorporation of more than one type of cross-coupling reaction have also been added to demonstrate the importance of these reactions in organic synthesis.

Recurrent Gastrointestinal Bleeding in an Elderly Patient With Peptic Ulcer Disease: Successful Management Through Multidisciplinary Intervention and Close Monitoring.

Upper gastrointestinal bleeding (UGIB) is a medical emergency with substantial morbidity and mortality worldwide. It is defined as bleeding originating in the gastrointestinal (GI) tract proximal to the ligament of Treitz and can be caused by various conditions, including peptic ulcers, gastritis, esophageal varices, Mallory-Weiss tears, and malignancies. Common complications include anemia, hemodynamic instability, perforation, and rebleeding. It is associated with high mortality and a poor prognosis, especially in high-risk populations. Management includes medical treatment, endoscopic intervention, endovascular arterial embolization, and surgery. We present an interesting case of an 87-year-old male with a history of duodenal ulcers who presented with a bleeding duodenal ulcer complicated by recurrent bleeding despite multiple hemostatic endoscopic interventions and arterial embolization. This case highlights the complexities involved in managing recurrent upper GI bleeding and emphasizes the significance of multidisciplinary approaches, timely interventions, and close monitoring.

Rare Sequelae of Endoscopic Retrograde Cholangiopancreatography: Polymicrobial Bloodstream Infection and Hepatic Abscess in an Elderly Individual.

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced technique using a side-viewing upper endoscope to diagnose and treat pancreaticobiliary diseases. ERCP is generally considered a safe procedure; however, it is associated with risks of certain complications such as pancreatitis, bowel perforation, bleeding, and infections. Very rarely, ERCP can result in abscess formation in different organs, such as the pancreas, liver, and intestines. Physicians should be vigilant for rare post-ERCP complications such as clinically significant bacteremia and hepatic abscess, especially in high-risk populations, as if left untreated, they can result in significant morbidity and mortality. We present an interesting and rare case of an 80-year-old patient who presented with nausea, vomiting, and abdominal pain post-ERCP and was found to have a polymicrobial bloodstream infection and a hepatic abscess. The patient was treated with medical therapy alone, with an appropriate clinical response.

Reverse Takotsubo Cardiomyopathy Triggered by Undiagnosed Right Adrenal Pheochromocytoma: A Rare Occurrence.

Takotsubo cardiomyopathy (TTC), also known as stress cardiomyopathy or broken heart syndrome, is a condition characterized by transient left ventricular dysfunction resembling myocardial infarction but without obstructive coronary artery disease. We present a rare case of a 59-year-old patient with cardiogenic shock (CS) caused by reverse TTC triggered by an undiagnosed right adrenal pheochromocytoma tumor. The patient initially presented with chronic headaches and difficulty breathing, and their condition rapidly deteriorated, necessitating intubation and inotropic support. Diagnostic tests confirmed the diagnosis of reverse TTC, and further investigation revealed an actively growing adrenal mass suggestive of a pheochromocytoma. The patient responded well to treatments, including the use of intra-aortic balloon pump support and subsequent weaning. A right adrenalectomy confirmed the presence of a pheochromocytoma. This case highlights the association between pheochromocytoma and reverse TTC, emphasizing the need to consider this rare etiology in patients presenting with CS. Long-term monitoring is crucial due to the risk of recurrence, even after tumor removal.

Stercoral Colitis: A Diagnostic Challenge and Therapeutic Approach in an Elderly Patient With Chronic Constipation.

Stercoral colitis, although rare, remains a significant cause of acute colonic inflammation. It is characterized by the presence of fecaloma leading to fecal impaction and subsequent mucosal injury, ultimately resulting in colonic wall inflammation. This condition primarily affects elderly patients with chronic constipation and is associated with significant morbidity and mortality if not recognized and managed promptly. Given its rarity and varied presentation, stercoral colitis often poses a diagnostic challenge. The clinical manifestations can mimic other colonic pathologies, such as diverticulitis, ischemic colitis, and inflammatory bowel disease, further contributing to diagnostic dilemmas. However, an astute clinician, armed with a high index of suspicion and the aid of advanced imaging techniques, can establish the correct diagnosis and initiate timely management. In this case report, we present a challenging case of stercoral colitis in an elderly patient with a history of chronic constipation. The aim of this report is to enhance awareness and understanding of this underdiagnosed condition among healthcare providers. Additionally, we discuss the clinical presentation, diagnostic workup, and therapeutic interventions employed to manage this formidable gastrointestinal entity.

Unmasking Non-small Cell Lung Cancer: The Unusual Trail of Hip Pain and Skeletal Metastasis.

We present a case of a 68-year-old female with a history of hypertension and hypothyroidism who presented to the emergency department with right lower extremity pain and difficulty ambulating. An initial evaluation revealed an abnormal appearance of the right hip on MRI, concerning avascular necrosis versus acetabular compression fracture. Subsequent diagnostic procedures, including joint aspiration and radiologic bone biopsy, led to the surprising discovery of metastatic lung carcinoma on tissue pathology. Further work-up reveals lung primary adenocarcinoma with additional metastases to the brain as well. The patient underwent resection of acetabulum and complex surgical pelvis reconstruction, irradiation for brain metastases, and rehabilitation. This case highlights the importance of considering atypical presentations of metastatic malignancies and the need for a multidisciplinary approach to optimize patient management.

Molecular insights into the pathogenic impact of vitamin D deficiency in neurological disorders.

Neurological disorders are the major cause of disability, leading to a decrease in quality of life by impairing cognitive, sensorimotor, and motor functioning. Several factors have been proposed in the pathogenesis of neurobehavioral changes, including nutritional, environmental, and genetic predisposition. Vitamin D (VD) is an environmental and nutritional factor that is widely distributed in the central nervous system's subcortical grey matter, neurons of the substantia nigra, hippocampus, thalamus, and hypothalamus. It is implicated in the regulation of several brain functions by preserving neuronal structures. It is a hormone rather than a nutritional vitamin that exerts a regulatory role in the pathophysiology of several neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and multiple sclerosis. A growing body of epidemiological evidence suggests that VD is critical in neuronal development and shows neuroprotective effects by influencing the production and release of neurotrophins, antioxidants, immunomodulatory, regulation of intracellular calcium balance, and direct effect on the growth and differentiation of nerve cells. This review provides up-to-date and comprehensive information on vitamin D deficiency, risk factors, and clinical and preclinical evidence on its relationship with neurological disorders. Furthermore, this review provides mechanistic insight into the implications of vitamin D and its deficiency on the pathogenesis of neurological disorders. Thus, an understanding of the crucial role of vitamin D in the neurobiology of neurodegenerative disorders can assist in the better management of vitamin D-deficient individuals.

Prolonged shoulder dysfunction after coronavirus disease vaccination: A case of shoulder injury related to vaccine administration.

Shoulder pain is a common symptom after intramuscular vaccination. However, only a few cases of shoulder joint injury have been reported after coronavirus disease 2019 vaccination. A 52-year-old woman experienced clinically significant pain in the left shoulder joint after receiving the first dose of a coronavirus disease 2019 vaccine. She neglected the shoulder pain, hoping that it would spontaneously improve without medical attention. However, the pain continued with obvious limitations in shoulder movement and function. After 8 months, she presented to the outpatient clinic with a frozen left shoulder. Such rare consequences of vaccinations, known as shoulder injury related to vaccine administration, can be prevented by using an appropriate needle gauge and length according to the patient's sex and weight with the correct injection site away from shoulder structures.

Evaluation of the health status outcome among inpatients treated for Amphetamine Addiction.

Amphetamine is one of the most abuser drugs in Saudi Arabia. The aim of this study was to evaluate health status outcome at baseline and after detoxification in amphetamine users through the evaluation of the body mass index, renal function tests, cardiac biomarkers, gonadal hormonal levels, and oxidative stress markers. A cross-sectional study was conducted on 90 participants. Sixty participants were hospitalized patients for treatment of addiction and 30 participants were healthy volunteers. This study was performed at a psychiatric and rehabilitation center, in Qassim region, in the Kingdom of Saudi Arabia. Participants were divided into: group I = control; group II = amphetamine users and group III = amphetamine plus cannabis users. Socio-demographic data was collected. The urinary amphetamine level, Severity Dependence Scale (SDS), body mass index (BMI), vital signs; serum levels of troponin T (TnT), immunoglobulin M (IgM), immunoglobulin G (IgG), luteinizing Hormone (LH), testosterone Hormone (TSTS), urea, creatinine, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured on admission and after detoxification. The results showed that the BMI was significantly decreased while, vital signs such as heart rate, blood pressure and respiratory rate were significantly increased in all abusers and returned to normal values after the detoxification period. The cardiac biomarker troponin T was significantly increased and reversed after detoxification. The immune system was evaluated through assessing serum levels of immunoglobulin (Ig) M and IgG. The immune system remained immunocompromised in drug users, and IgM and IgG levels did not reach the level of control group after treatment. Luteinizing and testosterone hormones were evaluated. Both hormones were increased on admission and improved after the detoxification period. Renal function showed no significant differences between drug users and the control group. In the evaluation of the antioxidant system, there was a significant increase in serum MDA, SOD, GPx, and CAT levels compared to healthy controls. After the detoxification phase, these oxidative stress biomarkers still remained elevated. The current results have shown the addiction of amphetamine and cannabis exert detrimental effects on different body organs and the exert major consequences on the health status of drug users. The present study showed that, there was no improvement in the levels of oxidative stress biomarkers, although an improvement was observed in the other parameters after the detoxification phase.

Probing the impact of conventional oil frying on the formation of polycyclic aromatic hydrocarbons in rabbit meat.

The study estimates, for the first time, the polycyclic aromatic hydrocarbons (PAHs) concentration (pyrene, fluoranthene, phenanthrene, anthracene, fluorene, and naphthalene) in rabbit meat samples. The study explores the effect of frying and the influence of cooking recipe (with or without condiments/additives) on different parts (hind legs, forelegs, and back), on PAH generation. A total of 36 meat samples on different parts from uncooked, cooked, chapli, and seekh kebabs were prepared and characterized by gas chromatography/mass spectrometry (GC/MS). PAHs data in all the samples indicate that cooking recipes (with and without additives/condiments) greatly affected the PAHs concentration. Significant concentrations of phenanthrene, fluoranthene, and naphthalene were formed in all the samples after cooking (frying) but naphthalene was dominant in terms of its concentration formed. A higher concentration of naphthalene was detected in the foreleg (4.56 µg/g) as well as in the hind leg (4.08 µg/g) seekh kebab (with additives), while foreleg chapli kebab (with additives) contained 1.44 µg/g PAH concentration. Frying is the processing methodology that causes the highest impact on PAHs. Contents of anthracene were detected only in the back (raw sample and chapli kebab), foreleg (without additives and seekh kebab), and hind leg (seekh kebab). In all rabbit meat samples, fluorene and pyrene were not identified.

Impact of different cooking methods on polycyclic aromatic hydrocarbons in rabbit meat.

The influence of a variety of cooking methods (poaching, boiling, grilling (charcoal or gas)), frying (pan, deep frying, and stir frying) with a variety of oils (vegetable oil, extra virgin olive oil, sesame oil, extra light olive oil, and sunflower oil), microwaving, and oven roasting on polycyclic aromatic hydrocarbons (PAHs) formation in rabbit meat samples was investigated. Meat samples (including three replicates) were prepared without additives or spices. PAHs extraction was carried out by saponification method with potassium hydroxide in methanol which was followed by a silica gel column technique and the samples were quantified by using gas chromatography with mass spectrometry (GC-MS). PAHs standards, fluorene, naphthalene, anthracene, phenanthrene, pyrene, acenaphthalene, fluoranthene, and benzopyrene, were used for this study. The other PAHs except fluorene were not observed (detection limit-0.009 µg/g) in all the samples. Among traditional processing techniques, higher PAH contents were observed as a result of frying. Frying with vegetable oil produced higher fluorene content (0.06-0.13 µg/g) in the deep-fried sample, although sesame oil is the best oil which produces lowest PAH contents in fried samples. Among all the processing techniques, lower fluorene (0.01-0.02 µg/g) content was noticed in poaching. Benzo(a)pyrene was not observed in all the investigated samples which is viewed as a reliable strategy of the cooking process for human consumption. After processing, the cooking loss was determined and oven roasting and grilling exhibited greater moisture loss.

Handwashing knowledge, attitudes, and practices during the COVID-19 pandemic in Saudi Arabia: A non-representative cross-sectional study.

Handwashing (HW) with water and soap is one of the cheapest and most effective ways of protecting oneself and others against the coronavirus. Here, the HW knowledge, attitudes, and practices of Saudi adults were assessed during the COVID-19 pandemic using a cross-sectional study conducted between May 8 and June 8, 2020, during a partial lockdown period. A web-based validated questionnaire was distributed through different social media platforms, and the sociodemographic characteristics of the participants, seven items related to knowledge, four items related to attitudes, and thirteen items related to the practice of HW were assessed. A total of 1323 (51% male and 49% female) adults from all regions of Saudi Arabia responded to the questionnaire. The overall mean (± SD) was 5.13 (± 1.18) for knowledge of HW and COVID-19, 2.79 (± 0.77) for attitude toward HW, and 7.8 (± 2.56) for HW practice. A multiple linear regression analysis revealed factors associated with knowledge to be age and family income. Sex, educational level, family income, and HW knowledge were associated with negative and neutral attitude, whereas age, sex, family income, and HW knowledge were associated with practice. These results suggest that HW knowledge was strongly associated with positive attitudes toward HW and correct HW practice in Saudi adults during the COVID-19 lockdown.

N-[4-(p-Toluenesulfonamido)phen-ylsulfon-yl]acetamide.

In the title compound, C(15)H(16)N(2)O(5)S(2), the dihedral between the two aromatic rings is 81.33 (6)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers, which are further connected via N-H⋯O hydrogen bonds into a chain running along [01].

Robust Anti-tumor Response in a Patient with Metastatic Gastroesophageal Junction Adenocarcinoma on Long-term Maintenance Chemotherapy With Trastuzumab Alone: An Unusual Occurrence.

Esophageal adenocarcinoma arises after a normal squamous mucosa undergoes metaplasia to the specialized columnar epithelium, which can then ultimately progress to dysplasia and subsequent malignancy. It typically presents at an advanced stage, and despite optimal management, the prognosis remains poor. Recently, the ToGA (Trastuzumab for Gastric Cancer) trial evaluated the role of trastuzumab (Herceptin®) in human epidermal growth factor receptor 2 (HER2) over-expressing gastric and gastroesophageal junction (GEJ) adenocarcinoma and showed improvement in overall survival when trastuzumab was added to the standard chemotherapy compared to standard chemotherapy without trastuzumab. However, data and experience are lacking in the literature regarding the use of trastuzumab outside of combination chemotherapy. The optimal length and safety of trastuzumab use as maintenance therapy in the long-term are also unclear in patients with gastric or GEJ adenocarcinomas after sustained remission. We report a case of metastatic GEJ adenocarcinoma, where the patient first showed an exceptional response to standard chemotherapy combined with trastuzumab and subsequently could sustain a long-lasting remission on maintenance therapy with trastuzumab alone. Trastuzumab was ultimately discontinued owing to the lack of clear knowledge regarding its length and safety of use as maintenance therapy in the long-term.

N'-(4-Bromo-phenyl-sulfon-yl)isonicotino-hydrazide.

The title compound, C(12)H(10)BrN(3)O(3)S, crystallizes with two crystallographically independent mol-ecules in the asymmetric unit. The dihedral angles between the two six-membered rings in the mol-ecules are 34.1 (3) and 45.1 (2)°. In the crystal structure, mol-ecules are connected via N-H⋯O and N-H⋯N hydrogen bonding.

Prevalence of blaTEM, blaSHV, and blaCTX-M Genes among ESBL-Producing Klebsiella pneumoniae and Escherichia coli Isolated from Thalassemia Patients in Erbil, Iraq.

BACKGROUND: Due to the recent appearance of organisms that are resistant to several drugs (multidrug-resistant) like Enterobacteriaceae that produce extended-spectrum ß-lactamase (ESBL, concerns have remarkably increased regarding the suitable treatment of infections. The present study was an investigation into ESBL molecular characteristics among clinical isolates of Klebsiella pneumoniae and Escherichia coli resulting in urinary tract infections (UTIs) and their pattern of antimicrobial resistance in order to come up with helpful information on the epidemiology of these infections and risk factors accompanied with them. METHODS: In order to conduct the study, 20 K. pneumoniae and 48 E. coli were isolated and retrieved from thalassemia center in Erbil, Iraq during July 2016 and September 2016. The collected strains were analyzed and the profile of their antimicrobial susceptibility was specified. In order to spot ß-lactamase genes (i.e. blaTEM, blaSHV, and blaCTX-M), polymerase chain reaction was conducted. RESULTS: The findings obtained from multiplex PCR assay showed that out of the collected strains of ESBL-producing E. coli, had 81% blaTEM, 16.2% blaSHV, and 32.4% blaCTX-M genes. Similarly, 64.7% blaTEM, 35.2% blaSHV, and 41.1% blaCTX-M genes existed in the isolates of K. pneumoniae. It was found that antibiotic resistance pattern of E. coli and K. pneumoniae isolates to 20 antibiotics varied widely. It was also concluded that the majority of the K. pneumoniae and E. coli isolates were multi-drug resistant (MDR). Moreover, 75% and 87.5% of respectively K. pneumoniae and E. coli isolates showed the MDR phenotypes. CONCLUSION: TEM prevalence was high among other types of ESBLs. Over all, the most active antimicrobial agents in vitro remained to be the carbapenems.

Comparison of the Effects of Metoprolol and Bisoprolol on Lipid and Glucose Profiles in Cardiovascular Patients.

BACKGROUND: Cardioselective beta-blockers may affect glucose or lipid profiles. OBJECTIVE: We sought to compare the effects of two beta-blockers, metoprolol and bisoprolol, as the most commonly used drugs in cardiology, on glucose and lipid profiles in patients with cardiovascular diseases. METHODS: We conducted a retrospective cross-sectional matched study at Prince Sultan Cardiac Center in Burydah in August 2017. Patient records were screened, and adult patients with cardiovascular disorders who were treated with a stable dose of metoprolol or bisoprolol were included. Parameters related to glucose and lipid metabolism were compared using the Student's t-test between the two groups. RESULTS AND CONCLUSION: The metoprolol and bisoprolol arms included 204 and 200 patients, respectively.

Health Impact of Domestic Violence against Saudi Women: Cross Sectional Study.

OBJECTIVE: Domestic violence is a major public health problem. A wide range of health hazards result from violence against women directly, or from its long-term consequences. The objective of this study is to determine health related consequences of domestic violence against women. METHOD: A community based cross-sectional study was carried through online survey; convenience sample was taken during the period between December 2013 and February 2014. 421 women completed the survey, who met the inclusion criteria and accepted willing to be a part of this study. The data was collected through online survey website. A validated Arabic version of NorVold Domestic Abuse Questionnaire (NOVAQ) was used as a tool to assess domestic violence among the study sample. Analysis was performed using SPSS, version 18.0. RESULTS: A total of 421 women participated in the survey. There was no significant correlation between socio-demographic characteristics and being abused or not. However, by further analysis we found more sexual abuse among non-working women P=0.048. There was significant correlation between abused women and general health status, doctor visits, depression, insomnia, and somatic symptoms. CONCLUSION: The consequences of abuse are profound, extending beyond the health of individual to affect the well-being of entire community. So, we recommend to increase community awareness through national awareness campaign, national prevalence survey of domestic violence and well trained health professionals for assessing domestic violence cases.

Comparative Study of Elemental Concentrations in the Scalp Hair and Nails of Myocardial Infarction Patients Versus Controls from Pakistan.

Ischemia heart disease has become a ubiquitous cause of morbidity and a leading contributor to mortality worldwide. The present study was aimed to quantify the elemental levels for Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Pb, Sr, and Zn in the scalp hair and nails of myocardial infarction (MI) patients and counterpart controls by flame atomic absorption spectrophotometry. The effects of elemental imbalances on the development of atherosclerosis were evaluated. Average concentrations of Pb (14.7 µg/g), Sr (21.6 µg/g), and Cr (3.70 µg/g) were significantly higher in the scalp hair of the patients, while those of Na, K, Mg, Fe, Mn, and Cd were measured at almost comparable levels in the scalp hair of the patients and controls. In the case of nail samples, average concentrations of Na (1260 µg/g), K (873 µg/g), Sr (70.9 µg/g), Cu (16.6 µg/g), and Mn (16.9 µg/g) were significantly higher in the patients than controls. The correlation study revealed significantly divergent mutual variations among the elements in MI patients and controls. Principal component analysis also manifested the diverse apportionment of the elements in both donor groups. Most of the elements revealed significant disparities in their concentrations based on gender, abode, and smoking habits of the donors in both groups. In conclusion, the elemental imbalance has potential proatherogenic effect that would have a significant impact on sensitive population groups.

Comparative Distribution, Correlation, and Chemometric Analyses of Selected Metals in Scalp Hair of Angina Patients and Healthy Subjects.

Numerous epidemiological studies are preponderance of evidences intimating development of coronary artery disease caused by metal imbalance. The present study was aimed to analyze Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Pb, Sr, and Zn in the scalp hair of angina patients and healthy subjects/controls employing HNO3-HCLO4-based wet digestion followed by quantification with atomic absorption spectrophotometry. The average concentrations of Cd, Cu, Cr, Fe, Mn, Pb, and Sr revealed significantly higher levels in scalp hair of patients than controls; however, Na and Zn were appreciably higher in healthy subjects. Dissimilarity in the trace metal distribution was also observed with gender, residence, dietary habits, and smoking habits of both donor groups. The correlation study and multivariate analyses revealed diverse mutual relationships and apportionment of the trace metals in the scalp hair of patients and controls.