Is Obesity a Risk Factor for Disorders of Amniotic Fluid?

OBJECTIVES: Prior studies show conflicting evidence as to whether obesity in the absence of other medical or pregnancy-related conditions contributes to amniotic fluid disorders. The purpose of this study is to determine the association between late-pregnancy obesity with oligohydramnios (amniotic fluid index [AFI] ≤5 cm or maximum vertical pocket [MVP] <2 cm) and/or polyhydramnios (AFI ≥24 cm or MVP ≥8 cm). METHODS: This is a retrospective cohort study of 961 women with singleton gestations who had one or more obstetrical ultrasounds at a single institution at 36 0/7 weeks gestation or beyond between August 1, 2015, and May 1, 2020. Patients were included if they had valid pregnancy dating and a documented AFI and/or MVP. Patients were categorized based on body mass index or BMI (eg, normal, overweight, Class I Obesity, Class II Obesity, or Class III Obesity). RESULTS: A total of 6.2% of patients met criteria for oligohydramnios based on AFI, MVP or both (n = 60). There was no significant association between oligohydramnios and increasing BMI, regardless of obesity class (P = .21). In terms of polyhydramnios, 5.6% of patients met criteria based on AFI, MVP, or both (n = 54). Similarly, there was also no significant association between polyhydramnios and increasing BMI, regardless of obesity class (P = .66). CONCLUSIONS: Elevated maternal BMI was not significantly associated with disorders of amniotic fluid, regardless of the severity of obesity.

Microwave-assisted synthesis of novel steroidal heterocyclic analogs as potent inhibitors of RANKL-induced osteoclastogenesis.

Osteoporosis is a significant public health issue in our aging population. It is an excessive bone resorption condition brought on by osteoclastogenesis, which makes bones more brittle. In the present work, a series of novel heterosteroidal derivatives have been synthesized using the microwave technique and were evaluated as antiosteoclastogenic agents. The structures of the newly synthesized compounds have been confirmed using analytical and spectral data. The antiosteoclastogenic activity of the newly synthesized compounds was estimated in vitro against osteoclast-differentiated cells from the RAW 264.7 cell line. The pregnenolone dimer 10, the pyridinotestosterone derivative 2, and the phenylnicotinonitrile pregnenolone derivative 8a attained the most promising antiosteoclastogenic activity displaying IC50 (the half maximal inhibitory concentration) values of 5.45 ± 5.30, 11.88 ± 2.09, and 13.40 ± 3.00 µM, respectively, in comparison with dimethyl itaconate (IC50 = 17.76 ± 3.20 µM) and alendronate (IC50 = 4.48 ± 1.89 µM) as reference compounds. Finally, an in silico ADME (Absorption, Distribution, Metabolism, and Excretion) study was conducted to evaluate the synthesized compounds' pharmacokinetic and drug-likeness properties. The results manifested that almost all the investigated compounds' properties were compatible with the specified optimal range, which indicates their reassuring pharmacokinetic properties.

Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity.

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine--C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3',2':4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 µM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3-49.0, 19.3-55.5, 22.7-44.8, and 36.8-70.7 µM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

Synthesis, molecular docking and antimicrobial activity of new fused pyrimidine and pyridine derivatives.

Synthesis of some new heterocyclic ring systems incorporated pyrimidine and pyridine moieties starting from 1-(furan-2-yl)-3-(thiophen-2-yl) chalcone was achieved. The structure of the new compounds was interpreted by spectral studies and ESI-MS analysis. Antimicrobial investigations of the designated compounds were performed towards some harmful pathogenic microbes. Antimicrobial tests proved that compound 11 unveiled a greater antimicrobial activity than other designed compounds. Docking of compound 11 into active site of DNA gyrase B chain displayed binding-energy of -13.05 kJ mol-1 and distance at 3.18 Ao. Furthermore, docking investigation was approved for the goal compounds into DNA gyrase B chain and exhibiting binding energy extended from -13.05 to -20.48 kJ mol-1.

Type 1 Narcolepsy in Pregnancy: A Case Report and Review of Literature.

Background Type 1 narcolepsy (with cataplexy) is a rare disorder affecting the central nervous system and is characterized by the inability to control sleep-wake cycles. There is a paucity of data regarding management during pregnancy. Case This is a 23-year-old primigravida with narcolepsy and cataplexy, treated with methylphenidate in the third trimester, resulting in an improvement of episodes of cataplexy. A review of the literature reveals information regarding options for medical management and the mode of delivery for these women. Conclusion Type 1 narcolepsy can be treated with medications after consideration of risks and benefits. For patients who are symptomatic at the time of birth, cesarean section may be the preferred mode of delivery in women with type 1 narcolepsy.

Oral manifestations of COVID-19 patients: An online survey of the Egyptian population.

OBJECTIVES: This pilot survey aims to study the oral manifestations associated with COVID-19 infection and report the prevalence of oral signs and symptoms in COVID-19 patients. MATERIALS AND METHODS: From May 15 to June 10, 2020, we used an online questionnaire containing the oral manifestations that are expected to be associated with the COVID-19 infection. Adults in our survey who have been diagnosed with COVID-19 positive were confirmed with reverse transcriptase PCR (RT-PCR), and isolated in various hospitals in Cairo, Egypt. RESULTS: This pilot study included 58 (53.4% males and 46.6% females) COVID-19 patients ages 18-46 years, and 13 (22.4%) were healthcare workers. Our results showed that 67.2% of the patients had at least one manifestation related to the oral cavity and salivary glands, and 32.8% (n = 19) did not have any symptoms associated with the oral cavity. The highest prevalence symptoms were dry mouth 39.7% (n = 23), gustatory dysfunction as 34.5% (n = 20) loss of salt sensation, 29.3% (n = 17) loss of sweet sensation, and 25.9% (n = 15) altered food taste, while the least prevalent symptoms were tongue redness 8.8% (n = 5), and gingival bleeding 7% (n = 4). The most frequently associated symptoms were loss of salt and sweetness, as reported by 27.6% of the participants. However, there was no significant association between the incidence of oral symptoms and demographic data (age, gender, or job) of the patients (p > 0.05). CONCLUSIONS: Based on limited data, COVID-19 significantly impacts the oral cavity and salivary glands, as salivary gland-related symptoms and taste disorders are highly prevalent in COVID-19 patients.

Synthesis of novel hybrid hetero-steroids: Molecular docking study augmented anti-proliferative properties against cancerous cells.

Hetero-steroids, hybrid anticancer agents, have received much interest in view of their numerous and promising biological activities. In this study, a novel class of hetero-steroids were synthesized, analytical and spectral data proved the validity of the novel synthesized steroid derivatives. The cytotoxicity of the synthesized compounds 2, 5, 6, 7, 10, 11, 12, 14, 15, 17 were evaluated using human hepatocellular carcinoma cell lines (HepG2 and Huh-7) and non-small cell lung cancer (A549) cell lines. The synthesized compounds reported a remarkable gradual decrease in the cell viability of the three tested cancer cell lines. It was observed that compounds 2 and 12 had the lowest IC50s and the highest cytotoxic effects against all tested cell lines. As attempt to explain the cytotoxic activity achieved by the tested compounds in the in vitro study, molecular simulation was done to reveal the activity of the tested compounds against four different proteins (CDK2, CYP19, JAK2, and BCL2) which are highly implicated in cancer regulation and progression. We found that compound 2, and 12 were the best docked compounds against all tested receptors, which was indicated by lowest binding energy compared to reference ligand. Interestingly enough, our molecular study was in agreement with the cytotoxic activity. As future prospective, we are recommending further study on compounds 2, and 12 against the four different proteins to prove their mode of action.

Design, Synthesis and Anticancer Activity of New Thiazole-Tetrazole or Triazole Hybrid Glycosides Targeting CDK-2 via Structure-Based Virtual Screening.

BACKGROUND & OBJECTIVE: The target tetrazole glycosides were synthesized by construction of ring system by cycloaddition reaction of benzothiazole-linked nitrile derivative and sodium azide followed by N-glycosylation process and deprotection. METHODS: The triazole glycosides were prepared by applying click approach involving dipolar cycloaddition of benzothiazole possessing alkyne functionality and different glycosyl azides. The products incorporating acyclic analogs of sugar moieties were synthesized through alkylation using acyclic oxygenated halides. RESULTS: The anticancer activity was studied against human breast adenocarcinoma cells (MCF-7) and human normal Retina pigmented epithelium cells (RPE-1). High activities were revealed by three compounds with IC50 values 11.9-16.5 µM compared to doxorubicin (18.6 µM) in addition to other four derivatives with good inhibition activities. CONCLUSION: Enzyme docking investigation was performed into cyclin-dependent kinase 2 (CDK2); a potential target for cancer medication. Compounds which have possessed highest activities revealed good fitting inside the binding site of the protein molecular surface and showed minimum binding energy.

Assessment of the Antitumor Potentiality of Newly Designed Steroid Derivatives: Pre-Clinical Study.

Cancer is recognized as one of the most prevalent contributors to mortality in several nations and it remains one of the common health issues globally. In particular, hepatocellular carcinoma (HCC) has become a public health problem along with the increase of hepatitis B (HBV) and hepatitis C (HCV) virus infections. Based on this fact, our study goaled to synthesize newly hybrid drugs containing heterocyclic rings incorporated to steroid moiety and to examine the potential antitumor activity of the newly designed heterosteroid derivatives against HCC induced in animal model. Several heterocyclic steroids were synthesized 2-7 and confirmed via the analytical and spectral data (IR, 1H NMR13C NMR and Mass spectroscopy). Compounds 3, 4, and 5 were chosen to be investigated as anticancer agents in HCC rat model by means of validated biomarkers (alfa -fetoprotein, endoglin, lipocali-2 and heat shock protein-70). Following administration of compounds 3, 4 or 5, availability of the active tumor marker molecules was significantly dropped and a substantial decrease of the angiogenic and inflammatory mediators was also evident. These findings were supported by the histological examination of liver tissue. Taken together, this study indicates the potential anticancer activity of the newly synthesized heterosteroid derivatives against HCC in vivo. The antitumor activity of these compounds was likely attributable to modulating some signal transduction pathways involved in tumorigenesis, angiogenesis and inflammation.

Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides.

BACKGROUND & OBJECTIVE: New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized. METHODS: The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation. RESULTS: The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin. CONCLUSION: Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

Synthesis and Evaluation of Novel Cholestanoheterocyclic Steroids as Anticancer Agents.

Modification of steroid molecules by introducing heterocyclic ring into the core structure of steroids has been utilized as an attractive approach for either cancer prognosis or diagnosis. Several new cholestanoheterocyclic steroids were synthesized, and analytical and spectral data proved the validity of the novel synthesized steroid derivatives. The cytotoxicity of synthesized compounds 3, 4, 5, 7, 9, 10, 13, 15b, and 16b was evaluated using human colorectal cancer HCT 116 and Caco-2, cervical cancer HeLa, hepatoma HepG2, and breast cancer MCF7 cell lines. Intriguingly, compound 13 has the highest cytotoxic effect when applied on the majority of cancer cells. In conclusion, compound 13 may be considered as a promising anticancer candidate against all cancer cell lines, because it recorded the lowest IC50 of the majority of the cancer cell lines used. Furthermore, a molecular docking study was employed to determine the binding modes against aromatase cytochrome P450 (CYP19), cyclin-dependent kinase 2 (CDK2), and B-cell lymphoma (BCL-2) proteins, which are major proteins involved in the pathogenesis of cancer. Molecular docking analyses revealed that compounds 13, 3, and 5 (free energy of binding = - 9.2, - 9.1, and - 9.0 kcal/mol, respectively) were the best docked ligand against aromatase CYP19; compounds 16b, 3, 9, and 10 (free energy of binding = - 9.6, - 9.3, and - 9.2 kcal/mol, respectively) were the best docked ligand against CDK2, while compounds 15b, 16b, and 13 (free energy of binding = - 9.1, - 9.0, and- 8.7 kcal/mol, respectively) were the best docked ligand against BCL2. In conclusion, compounds 3, 13, and 16b were the most promising compounds with the lowest IC50s against most of the tested cancer cell lines, and they displayed the lowest binding energies, critical hydrogen bonds, and hydrophobic interactions with the three molecular targets compared to other tested compounds.

Maternal and neonatal outcomes after attempted suicide.

OBJECTIVE: The purpose of this study was to describe identifiers and estimate maternal and neonatal outcomes in women who attempt suicide during pregnancy. METHODS: A linked Vital Statistics-Patient Discharge database of the State of California was used to identify cases of intentional injury during pregnancy. A retrospective analysis of maternal and neonatal outcomes in pregnant women who were admitted for attempted suicide is presented. RESULTS: There were 4,833,286 deliveries in California from 1991 to 1999. Of those deliveries, 2,132 were complicated by attempted suicide during pregnancy (0.4 per 1,000 pregnancies). The control population was composed of patients who did not attempt suicide. The group of women that attempted suicide during pregnancy had increases in premature labor, cesarean delivery, and need for blood transfusion. Analysis of neonatal outcomes revealed increases in respiratory distress syndrome and low birth weight infants. A subanalysis, including women who delivered at the hospitalization for attempted suicide, demonstrated increased premature delivery, respiratory distress syndrome, and neonatal and infant death. CONCLUSION: Attempted suicide is associated with significantly higher rates of maternal and perinatal morbidity, and in some cases, perinatal mortality. The best identifier for women at risk for attempting suicide is substance abuse. Care provider identification and prevention are of key importance in preventing these outcomes.

Obstetric outcomes in women with elevated maternal serum human chorionic gonadotropin.

OBJECTIVE: This study was undertaken to assess outcomes in unselected women with maternal serum human chorionic gonadotropin (MShCG) 2.0 MoM or greater. STUDY DESIGN: This is an observational cohort study of 309 women with MShCG 2 MoM or greater and 309 women of the same age and ethnicity with MShCG less than 2.0 MoM who were evaluated for preterm delivery (PTD), preeclampsia, stillbirth, birth weight 10% or less, and birth weight 90% or greater (larger for gestational age [LGA]). Confounding variables evaluated were nulliparity, prior PTD, chronic hypertension, diabetes, and maternal serum alpha-fetoprotein and estriol. RESULTS: There was no overall increase in adverse outcomes despite associations found with PTD for preeclampsia with MShCG 3.0 MoM or greater (odds ratio [OR] 5.9, CI 1.5-23.2) and PTD for fetal indications with MShCG 4.0 MoM or greater (OR 45.5, CI 4.1-509). There was an increase of LGA infants with MShCG 3.0-3.9 MoM (OR 2.5, CI 1.0-5.8). CONCLUSION: Adverse pregnancy outcome is associated with MShCG 3.0 MoM or greater, thus increased surveillance is not warranted with lower values.

Association of maternal fractures with adverse perinatal outcomes.

OBJECTIVE: We sought to assess the effects of fracture injuries on maternal and fetal/neonatal outcomes in a large obstetric population. STUDY DESIGN: We performed a retrospective cohort study using a database in which maternal and neonatal hospital discharge summaries were linked with birth and death certificates to identify any relation between maternal fractures and maternal and perinatal morbidity. Fracture injuries and perinatal outcomes were identified with the use of the International Classification of Diseases, 9th revision, Clinical Modification codes. Outcomes were further subdivided on the basis of anatomic site of fracture. RESULTS: A total of 3292 women with > or = 1 fractures were identified. Maternal mortality (odds ratio, 169 [95% CI, 83.2,346.4]) and morbidity (abruption and blood transfusion) rates were increased significantly in women who were delivered during hospitalization for their injury. Women who were discharged undelivered continued to have delayed morbidity, which included a 46% increased risk of low birth weight infants (odds ratio, 1.5 [95% CI, 1.3,1.7]) and a 9-fold increased risk of thrombotic events (odds ratio, 9.2 [95% CI, 1.3,65.7]) Pelvic fractures had the worst outcomes. CONCLUSION: Fractures during pregnancy are an important marker for poor perinatal outcomes.

Maternal and neonatal outcomes of assaults during pregnancy.

OBJECTIVE: To assess perinatal outcomes of women hospitalized for assault during pregnancy as a function of timing of delivery. METHODS: A retrospective population-based study analyzing maternal discharge records linked to birth/death certificates in California from 1991 to 1999 was performed. International Classifications of Disease, Ninth Clinical Modification (ICD-9-CM) codes were used to identify injury types and outcomes. External causation codes identified assaults as the mechanism of the injuries. Injury Severity Scores were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and multivariate logistic regression was used for analysis of outcomes. RESULTS: A total of 2,070 women were hospitalized during pregnancy after sustaining an assault. Assaulted women were younger, multiparous, and with delayed prenatal care compared with unassaulted controls. Women delivering at the assault hospitalization had high rates of prematurity: 24%, OR 2.4 (95% CI 1.8-3.3), maternal death: 0.71%, OR 19 (95% CI 2.7-144.7), fetal death: 9.3%, OR 8 (95% CI 4.6-14.3), uterine rupture: 0.71%, OR 46 (95% CI 6.5-337.8), and other adverse outcomes compared with unassaulted women. Women discharged after an assault, delivering at a subsequent hospitalization, had increased risks of abruption: 2%, OR 1.8 (95% CI 1.3-2.5), hemorrhage: 3.2%, OR 1.8 (95% CI 1.4-2.5), prematurity: 15%, OR 1.3 (95% CI 1.2-1.5), and low birth weight: 13.4%, OR 1.7 (95% CI 1.5-1.9) at delivery. CONCLUSION: Women sustaining an assault during pregnancy experience both immediate (uterine rupture, increased fetal and maternal mortality) and long-term sequelae (prematurity and low birth weight infants), which have significant negative effects on pregnancy outcome. LEVEL OF EVIDENCE: III.

Synthesis of novel steroidal curcumin derivatives as anti-Alzheimer's disease candidates: Evidences-based on in vivo study.

Alzheimer's disease (AD) is a complex disease in which a single monofunctional 'targeted' drug is uneffective for management. Hybrid drugs that impact multiple targets simultaneously are better at controlling such complex disease systems. Hybrid agents were synthesized through the combination of the steroid moiety with curcumin molecule. Also novel curcumin analogues containing promising heterocyclic nucleus fused to the essential pharmacophoric feature of the curcumin moiety, were synthesized. The aim of the present study was extended to elucidate the efficacy of these novel synthesized compounds in the regression of AD induced in adult female albino rats. The results revealed that treatment of AD groups with compounds 3, 5, 8c or rivastigmin experienced significant increase in brain Ach, GSH, paraoxenase and BCL2 levels with respect to untreated group associated with significant decrease in brain AchE activity, urinary 8-OHG level, serum Caspase-3 level and brain P53 level relative to the untreated group. Immunohistochemical investigation revealed that the selected treatments caused marked increase in ChAT positive cells. These findings were documented by the histological investigation of the brain tissue. The activity of tested compounds showed gradual increase from compound b followed by compound 8c then compound 5. The anti-cholinesterase potential, anti-oxidant properties and anti-apoptotic activity are responsible for the anti-Alzheimer's disease potential of these compounds.

Perinatal outcomes of traumatic injuries during pregnancy.

Traumatic injuries although uncommon (affect 6% to 7% of all pregnancies) are associated with poor maternal, fetal, neonatal, and infant outcomes. The magnitude of the problem is most likely largely underestimated secondary to lack of standardized reporting. Newer data are available that stratify maternal risk by type of injury sustained, and may assist in evaluation of the pregnant trauma victim. Long-term adverse events after maternal discharge for a traumatic injury are emerging, and suggest closer monitoring of the patient for preterm labor, growth restriction, and placental abruption during the affected pregnancy.

Trauma during pregnancy: an analysis of maternal and fetal outcomes in a large population.

OBJECTIVE: This study was undertaken to determine the occurrence rates, outcomes, risk factors, and timing of obstetric delivery for trauma sustained during pregnancy. STUDY DESIGN: This is a retrospective cohort study of women hospitalized for trauma in California (1991-1999). International Classification of Disease, ninth revision, Clinical Modification codes, and external causation codes for injury were identified. Maternal and fetal/neonatal outcomes were analyzed for women delivering at the trauma hospitalization (group 1), and women sustaining trauma prenatally (group 2), compared with nontrauma controls. Injury severity scores and injury types were used to stratify risk in relation to outcome. Statistical comparisons are expressed as odds ratios (ORs) with 95% CIs. RESULTS: A total of 10,316 deliveries fulfilling study criteria were identified in 4,833,286 total deliveries. Fractures, dislocations, sprains, and strains were the most common type of injury. Group 1 was associated with the worst outcomes: maternal death OR 69 (95% CI 42-115), fetal death OR 4.7 (95% CI 3.4-6.4), uterine rupture OR 43 (95% CI 19-97), and placental abruption OR 9.2 (95% CI 7.8-11). Group 2 also resulted in increased risks at delivery: placental abruption OR 1.6 (95% CI 1.3-1.9), preterm labor OR 2.7 (95% CI 2.5-2.9), maternal death OR 4.4 (95% CI 1.4-14). As injury severity scores increased, outcomes worsened, yet were statistically nonpredictive. The type of injury most commonly leading to maternal death was internal injury. The risk of fetal, neonatal, and infant death was strongly influenced by gestational age at the time of delivery. CONCLUSION: Women delivering at the trauma hospitalization (group 1) had the worst outcomes, regardless of the severity of the injury. Group 2 women (prenatal injury) had an increased risk of adverse outcomes at delivery, and therefore should be monitored closely during the subsequent course of the pregnancy. This study highlights the need to optimize education in trauma prevention during pregnancy.