Anti-Müllerian hormone and response to ovulation induction with clomiphene citrate in women with polycystic ovary syndrome

Background: Anti-Müllerian hormone (AMH) is suggested as an important marker for women with polycystic ovary disease (PCOS). Several studies have found serum level of AMH correlate well to ovarian response to ovulation induction in women with PCOS. This study was conducted to assess the relationship between AMH in women with PCOS and response to ovulation induction with clomiphene citrate.Methods: Prospective observational cohort study conducted at Ain-Shams university maternity hospital from February 2013 to February 2014. 100 women with PCOS were recruited from the infertility outpatient clinic. Serum AMH levels were measured by enzyme linked immunosorbent assay in the early follicular phase (days 3-5). Ovulation induction by clomiphene citrate was started on day 5 as 50 mg daily tablet for 5 days. Ovulation was documented by transvaginal ultrasonography and women who failed to ovulate till day 35 were considered anovulatory.Results: 72 women ovulated within 12 to 33 days of the menstrual cycle, while 28 had undetectable ovulation till day 35. The median serum AMH level was significantly higher in women with failed ovulation [4.05 ng/mL (3.7 - 4.4)] than in ovulating women [2.7 ng/mL (1.9 - 3.1)] (p<0.001). Receiver-operating characteristic (ROC) curve analysis found the best cutoff value of AMH for prediction of successful ovulation ≤3.6 ng/mL (sensitivity = 97.2%, specificity = 82.1%).Conclusions: Anti-Müllerian hormone is a very useful predictor of poor responders to clomiphene citrate among women with polycystic ovary disease

Derivatization and biological activity studies of 3-chloro-3-chlorosulfenyl spiro tetrahydropyran/tetrahydrothiopyran-4,2'-chroman-4'-one

1502-1510The adducts 4a,b-7a,b have been obtained either by reducing α-chloro-β-oxosulfenyl chlorides 2a,b with iodide ion in the presence of dienes namely, 2-methyl-1,3-butadiene (isoperene), 2,3-dimethyl-1,3-butadiene, 1,2,3,4- tetrachlorocyclopentadiene, or 1,3-cyclohexadiene, respectively; or by thermolysis of oxadithiin derivatives 3a,b in the presence of the same aforementioned dienes presumably via the formation of the same intermediate A in both cases of compounds 2a,b and 3a,b. It is observed that α-chloro-β-oxosulfenyl chlorides 2a,b undergo straight forward substitution with potassium cyanide to give 8a,b. Direct oxidation of 2a,b with H2O2/AcOH affords 3,3-dichloropyran-4-ones 9a,b, while conversion of 2a,b to the sulfonamides 10a,b followed by oxidation provides 3-chloropyranones 11a,b. Antioxidant and antimicrobial evaluation of compounds 4a,b-6a,b shows moderate activiy. MIC of the derivative 6b reveals a remarkable inhibition of the pathogenic gram positive bacteria (Staphylococcus aureus ) as well as gram negative E coli

Derivatization and biological activity studies of 3-chloro-3-chlorosulfenyl spiro tetrahydropyran/tetrahydrothiopyran-4,2'-chroman-4'-one

The adducts 4a,b-7a,b have been obtained either by reducing α-chloro-β-oxosulfenyl chlorides 2a,b with iodide ion in the presence of dienes namely, 2-methyl-1,3-butadiene (isoperene), 2,3-dimethyl-1,3-butadiene, 1,2,3,4-tetrachlorocyclopentadiene, or 1,3-cyclohexadiene, respectively; or by thermolysis of oxadithiin derivatives 3a,b in the presence of the same aforementioned dienes presumably via the formation of the same intermediate A in both cases of compounds 2a,b and 3a,b. It is observed that α-chloro-β-oxosulfenyl chlorides 2a,b undergo straight forward substitution with potassium cyanide to give 8a,b. Direct oxidation of 2a,b with H2O2/AcOH affords 3,3-dichloropyran-4-ones 9a,b, while conversion of 2a,b to the sulfonamides 10a,b followed by oxidation provides 3-chloropyranones 11a,b. Antioxidant and antimicrobial evaluation of compounds 4a,b-6a,b shows moderate activiy. MIC of the derivative 6b reveals a remarkable inhibition of the pathogenic gram positive bacteria (Staphylococcus aureus ) as well as gram negative E coli.

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Fragmented QRS complex, highly sensitive CRP, and fibrinogen in early detection of asymptomatic cardiac involvement in systemic lupus erythematosus

Abstract Background Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular illnesses. Asymptomatic affection might exist, so early diagnosis can improve the outcome. Aim The purpose of this study was to determine the importance of highly sensitive C-reactive protein, fragmented QRS, and fibrinogen levels in identifying subclinical cardiac involvement in SLE patients, as well as how these variables relate to disease activity. Results Regarding hs-CRP and fibrinogen, there were significant differences between the SLE and control group, with a higher frequency of fQRS in the lupus group. The lupus group was divided into 2 subgroups: 44 patients with fragmented QRS in ECG (83%) and 9 patients with normal QRS (17%) with a higher mean value of hs-CRP and fibrinogen level (58.76 ± 70.15, 18.54 ± 26.79) and low HDL (53.37 ± 10.37) in those with fQRS ( +). The sensitivity and specificity of hs-CRP at a cut of level (3.5 mg/L) for fQRS in SLE patients were 75.5%, and 71.7%, respectively. Regression analysis showed hs-CRP and were significant predictors for fQRS changes in SLE patients. Conclusions A more thorough evaluation of SLE patients with fQRS complexes with hs-CRP and fibrinogen is important with close follow-up for the detection of subclinical cardiac involvement in SLE. Also, SLE activity is linked to fQRS and fibrinogen. Therefore, we advise using them for additional medical care for lupus

Polyphenol-Rich Extracts and Essential Oil from Egyptian Grapefruit Peel as Potential Antioxidant, Antimicrobial, and Anti-Inflammatory Food Additives

Grapefruit (GF) processing generates significant nutrient and economic losses due to the production of 50% by-products, primarily peels. GF peels are a rich and sustainable source of bioactive compounds (BCs), such as essential oils (EOs) and phenolic compounds. Thus, finding value-added solutions based on a circular economy is paramount. This research aims to assess the antioxidant, anti-inflammatory, and antimicrobial properties of a hydroethanolic polyphenol-rich extract from crude GF peels (GF-CE), essential oil (GF-EO), and polyphenol-rich extract from GF peels after essential oil extraction (GF-PE). The GF-CE and GF-PE showed high concentrations of naringenin (7.71 and 48.60 mg/g dry extract (DE)), narirutin (15.03 and 28.73 mg/g DE), and hesperidin (0.67 and 0.29 mg/mL), respectively. Extracting firstly EOs from GF improved the release of phenolic acids (p-coumaric, ferulic, and chlorogenic acid). The GF-CE exhibited stronger free radical scavenging activity mainly in DPPH (IC50 = 75.69 ± 0.81 µg/mL) than GF-EO (1271 ± 0.85 µg/mL) and GF-PE (113.45 ± 0.85 µg/mL). The GF-EO demonstrated moderate antimicrobial activity against Gram-positive bacteria compared to the reference standard (amoxicillin) and strong activity against the yeast Candida albicans (inhibition zone of 16 mm). The major compounds in the GF-EO included D-limonene (25%), nootkatone (24%), and β-pinene (8%). Both polyphenol-rich extracts showed promising activities as COX1 and COX2 inhibitors with IC50 values of 25 ± 0.1 and 0.28 ± 0.00 µg/mL (compared to celecoxib (97.5 ± 0.1 and 0.31 ± 0.01 µg/mL) and indomethacin (6.25 ± 0.00 and 0.52 ± 0.01 µg/mL) as the standards), respectively. The study concludes that GF peels are a valuable source of BCs with significant bioactivities, offering a sustainable multi-cascade approach to recovering value-added compounds from GF peels in alignment with circular economy principles and open opportunities as functional ingredients for food applications

Incidence of bone fractures among patients on maintenance hemodialysis

AbstractBackground Patients with chronic kidney disease, especially those undergoing hemodialysis (HD), have a higher risk of fragility fractures. However, the magnitude of the problem and risk factors associated with fracture incidence have not been well studied in the Kingdom of Saudi Arabia.Methods This multicenter retrospective study involved HD centers in Jeddah from 2015 to 2021. This study included all adult HD patients. Patient demographics, medication usage, and clinical and biochemical parameters were collected from the registry records.Results The study included 328 patients on HD, with a mean age of 53 years. The median duration of HD was 47 months. Osteoporosis was found in 9% of the patients, and 8% had a previous parathyroidectomy. Over the observation period, fractures occurred in 32 patients, with an incidence rate of 20 case/1000 end stage kidney disease patients-year. Patients with fractures had a higher rate of osteoporosis, underwent more parathyroidectomy, had longer HD vintage, and higher bone-specific alkaline phosphatase (BSAP) levels. BSAP was the most significant predictor of fracture incidence in the regression analysis. Using a BSAP cutoff value of 96.6 µg/L, the sensitivity and specificity to predict fractures were 81.8% and 49%, respectively.Conclusion The main risk factors for incident fractures were osteoporosis, previous parathyroidectomy, longer HD vintage, and higher BSAP level. A higher BSAP score was the most significant predictor of incident fractures. This may highlight the importance of monitoring bone turnover markers and the negative impact of high bone turnover on patient health

Production, Bioprocessing and Anti-Proliferative Activity of Camptothecin from Penicillium chrysogenum, &ldquo;An Endozoic of Marine Sponge, Cliona sp.&rdquo;, as a Metabolically Stable Camptothecin Producing Isolate

Exploring the metabolic potency of fungi as camptothecin producers raises the hope of their usage as an industrial source of camptothecin, due to their short-life span and the feasibility of metabolic engineering. However, the tiny yield and loss of camptothecin productivity of fungi during storage and sub-culturing are challenges that counteract this approach. Marine fungi could be a novel source for camptothecin production, with higher yield and reliable metabolic sustainability. The marine fungal isolate Penicillium chrysogenum EFBL # OL597937.1 derived from the sponge &ldquo;Cliona sp.&rdquo; has been morphologically identified and molecularly confirmed, based on the Internal Transcribed Spacer sequence, exhibiting the highest yield of camptothecin (110 &mu;g/L). The molecular structure and chemical identity of P. chrysogenum derived camptothecin has been resolved by HPLC, FTIR and LC-MS/MS analyses, giving the same spectroscopic profiles and mass fragmentation patterns as authentic camptothecin. The extracted camptothecin displayed a strong anti-proliferative activity towards HEP-2 and HCT-116 (IC50 values 0.33&ndash;0.35 &micro;M). The yield of camptothecin was maximized by nutritional optimization of P. chrysogenum with a Plackett-Burman design, and the productivity of camptothecin increased by 1.8 fold (200 &micro;g/L), compared to control fungal cultures. Upon storage at 4 &deg;C as slope culture for 8 months, the productivity of camptothecin for P. chrysogenum was reduced by 40% compared to the initial culture. Visual fading of the mycelial pigmentation of P. chrysogenum was observed during fungal storage, matched with loss of camptothecin productivity. Methylene chloride extracts of Cliona sp. had the potency to completely restore the camptothecin productivity of P. chrysogenum, ensuring the partial dependence of the expression of the camptothecin biosynthetic machinery of P. chrysogenum on the chemical signals derived from the sponge, or the associated microbial flora. This is the first report describing the feasibility of P. chrysogenum, endozoic of Cliona sp., for camptothecin production, along with reliable metabolic biosynthetic stability, which could be a new platform for scaling-up camptothecin production