Base/Solvent Controlled Divergent Synthesis of Norbornane-Fused Dihydrophenanthrenes and Triphenylenes via Palladium Catalyst.

A base/solvent controlled divergent synthesis for the construction of polycyclic hydrocarbons has been developed. In this process, norbornene through a reagent role leads to the synthesis of norbornane-fused dihydrophenanthrenes, which are essential due to their biological activities. Amazingly, by switching solvent and base, the role of norbornene becomes limited to a mediator/catalyst; therefore, it is removed from the final scaffold, and triphenylenes are regioselectively synthesized. Additionally, by removing norbornene from the reaction conditions, a different path leading to synthesis of unsymmetrically substituted triphenylenes with exceptional regioselectivity is established. This reaction includes a rare domino decarboxylation/C-H activation/annulation in a chemo- and regioselective manner.

Maternal and Neonatal Outcomes of COVID-19 Infection in Pregnancy.

BACKGROUND: Limited data is available on the full spectrum of maternal COVID-19 infection in terms of pregnancy outcomes. The present study aimed to compare the maternal and neonatal outcomes of COVID-19 in infected and non-infected pregnant women. METHODS: A dual-site retrospective cohort study was conducted in two tertiary hospitals in Isfahan, Iran. The sample included 104 infected and 210 non-infected hospitalized pregnant women. Odds ratios (OR) were estimated using multivariate logistic regression. RESULTS: There were significant differences between COVID-19-infected and non-infected pregnant women regarding preterm labor (PTL) (odds ratio [OR]: 11.34, 95% confidence interval [CI]: 1.19-48.54, P=0.035); hospitalization days (OR: 7.21, 95% CI: 4.05-12.85, P≤0.001); cesarean section (CS) (OR: 4.76, 95% CI: 1.78-12.45, P=0.002); neonatal admission to neonatal intensive care unit (NICU) (OR: 1.28, 95% CI: 1.12-1.67, P=0.004); and neonatal respiratory distress (OR: 2.37, 95% CI: 1.02- 5.47, P=0.044). No significant association was found between COVID-19 infection and abortion (OR: 0.06, 95% CI: 0.01-1.45, P=0.084); stillbirth (OR: 1.84, 95% CI: 0.05-39.68, P=0.743); Apgar score (1 minute) (OR: 0.91, 95% CI: 0.74-1.13, P=0.382); Apgar score (5 minutes) (OR: 0.97, 95% CI: 0.81-1.18, P=0.765); and low birth weight (LBW) (OR: 4.76, 95% CI: 1.78-12.45, P=0.002). CONCLUSION: PTL, CS, neonatal admission in NICU, neonatal respiratory distress, and hospitalization days were significantly higher in pregnant women with COVID-19 compared to those without infection.

Remdesivir Prescription in Pregnant Women Infected with COVID-19: A Report of Compassionate Use.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease that the physiological changes in pregnancy can make pregnant patients more susceptible to more severe forms of this infection. Hence, the treatment of COVID-19 in pregnant women can be challenging. This study was designed to evaluate the safety and efficacy of Remdesivir in pregnant women with COVID-19. Materials and Methods: This study was conducted on 150 pregnant women with moderate to severe COVID-19 infection. Remdesivir was prescribed and continued for 5 or 10 days according to the patient's condition. Maternal and pregnancy outcomes and also recovery rates were evaluated. Moreover, additional variables were examined: age, gestational age, symptoms, O2 saturation and laboratory tests at admission, the interval between symptom initiation and admission to hospital and Remdesivir prescription, hospitalization days, and ICU admission. Results: The mean age was 32.37 years. Cough and dyspnea were the most prevalent symptoms (74% and 68.7%, respectively). At the time of admission, 79 (52.7%) women needed low-flow oxygen support, 67 (44.7%) needed high-flow oxygen support, and 4 (2.7%) were intubated. Fifty-four (36%) patients required ICU care. In patients who died (12 women), Remdesivir was prescribed later than those discharged (P value, 0.04). Patients with favorable pregnancy outcomes received Remdesivir earlier than those with unfavorable pregnancy outcomes (P value: 0.008). The recovery rate was 70% (89.9% in the low-flow oxygen, 50.7% in the NIPPV/high flow oxygen, and 0% in the intubated women). Conclusion: The results suggest that the early prescription of Remdesivir in pregnant women with moderate COVID-19 can improve the outcomes.

Syn- versus anti-carbopalladation of alkynes with organoborons: access to indoles symmetrically and unsymmetrically substituted on their 2,3-positions.

A palladium (II)-catalyzed borono-ortho-CH activation/amination cascade for the construction of two C-N bonds and one C-C bond in a single synthetic sequence is reported. This method proceeds through a formal syn-carbopalladation of alkynes with organoboron compounds, forming alkenyl palladium species, which are trapped by simple amines to provide highly substituted indoles. Remarkably, with an electron-rich arylboronic acid, the reaction proceeds through an unexpected anti-carbopalladation terminated by ortho-CH activation of diarylalkyne/amination reaction to provide an unsymmetrically substituted 2,3-diaryl indole instead. In the follow-up chemistry, we demonstrate that urea participates in this cascade to offer a variety of free NH-indoles.

A Lesson for the Future; Determining the Prognosis of the Pregnant Patients with COVID-19 in the Second Trimester? A Case Report.

Background: Coronavirus disease 2019 (COVID-19), the third coronavirus epidemic outbreak, has brought about a lot of concern about the pregnancy and the disease course, fatality rate, and the best management in severe cases. Early April 27, 2020, the first maternal mortality due to progressive COVID-19 infection was reported. Considering this challenging situation, the need for some comprehensive data on the main risk and predictive factors of disease progression is clear. Case Presentation: Here, we present our experience with 4 confirmed pregnant cases of COVID-19 in the second trimester, who showed typical COVID-19 symptoms like fever, cough, and myalgia. We aim to compare our findings with prior reports by reviewing the most recent and relevant studies.4 cases of COVID-19 induced respiratory discomfort in the second trimester of pregnancy were admitted to the intensive care unit. Most of the cases showed respiratory failure that led to intubation, but despite the similar initial presentation, they revealed widely. All of the required medical records are described here. Conclusion: Considering the limited information on this new COVID-19 clinical courses in pregnancy in comparison with two prior coronavirus outbreaks since the early 21 century, SARS-Cov and MERS-Cov, the possibility of poor pregnancy outcome has been confirmed, but there is debate on the effect of pregnancy and different management on disease progression. Taking into account the avail of this finding, our experiences, against prior belief, suggest pregnant patients are susceptible to severe morbidity and mortality, similar to report on pregnancies with SARS and MERS.

Lysophosphatidic Acid Alters The Expression of Apoptosis Related Genes and miR-22 in Cultured and Autotransplanted Ovaries.

OBJECTIVE: The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) on the follicular development, incidence of cell death, and expressions of apoptosis related genes and miR-22 in transplanted ovaries. MATERIALS AND METHODS: In this experimental study, three-week-old mice ovaries were cultured for 24 hours in the presence and absence of LPA, and we assessed cell survival and normal follicular rates in some of the cultured ovaries. The remaining cultured ovaries were autotransplanted in the presence and absence of LPA as four experimental groups (LPA-/LPA-, LPA-/LPA+, LPA+/LPA-, LPA+/LPA+). The follicular development, immunohistochemistry for BAX, and expressions of genes related to apoptosis and miR-22 by real time reverse transcription polymerase chain reaction (RTPCR) were studied at the first oestrous cycles in the recovered ovaries. Sera 17-ß-oestradiol (E2) and progesterone (P4) levels were also assessed. RESULTS: Both cell survival and normal follicular rates were significantly higher in cultured ovaries in the presence of LPA after 24 hours (P<0.05). There was an increase in follicular development in comparison with the intact control group in the four transplanted groups (P<0.05). The LPA+/LPA- group had significantly higher follicular development, a decline in BAX positive cells, and a decrease in pro-apoptotic gene expressions in parallel with enhanced expression of anti-apoptotic and miR-22 genes and higher levels of hormones compared with the non-treated and intact control groups (P<0.05). CONCLUSION: LPA, as a survival factor, improves follicular development in transplanted ovaries by providing a balance between the anti- and pro-apoptotic genes in association with an increase in miR-22 expression.

Effect of Lysophosphatidic Acid on the Vascular Endothelial Growth Factor Expression in Autotransplanted Mouse Ovaries Encapsulated in Sodium Alginate.

Objective: The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) supplementation during in vitro culture and transplantation of mouse ovaries on the follicular development and expression of vascular endothelial growth factor (VEGF) as an angiogenesis factor at the mRNA and protein levels. Materials and methods: Three weeks old mice ovaries were cultured in the presence and absence of LPA for 24 hours, then they were capsulated in sodium alginate in the presence and absence of LPA as four experimental groups. After transplantation the vaginal smears were performed daily to evaluate the initiation of the estrous cycle. The morphology and follicular distribution were analyzed at the first and fourth estrous cycles using hematoxylin and eosin staining. Then in the groups that showed higher and lower follicular development the immunohistochemistry assay was conducted to identify VEGF protein expression, and the real time RT-PCR was done to analyze the expression of Vegf gene at the first estrus cycle. Results: The large size follicles and also the corpus luteum were prominent in all transplanted groups at fourth estrus cycle in comparison with intact control groups. The statistically lowest percentage of small size follicles and the highest percentages of large size follicles were seen in LPA+/LPA- group (p<0.05). The expression ratio of Vegf to ß-actin was significantly higher in this group in comparison with non-LPA treated and intact control groups (p <0.05). Conclusion: LPA as an angiogenesis factor increases the follicular development in transplanted ovaries but it causes early discharge of ovarian reserve.

Follicular development and the expression of BAX and vascular endothelial growth factor in transplanted ovaries in uni- and bilateral ovariectomized mice: An experimental study.

BACKGROUND: Several conflicting results have been reported on the survival and function of transplanted ovaries. OBJECTIVE: Evaluation of the follicular development and the expression of vascular endothelial growth factor (VEGF) and Bcl-2-associated X protein (BAX) in ovaries transplanted into uni- and bilaterally ovariectomized mice. MATERIALS AND METHODS: In this experimental study, 40 female NMRI mice (21-days-old, 12-15 gr) were ovariectomized uni- and bilaterally (n = 20/ group), while the 8-wk-old mice were considered as intact control group (n = 6). 5 weeks after transplantation at the proestrus stage, the morphology of recovered transplanted ovaries and the proportion of follicles were studied at different developmental stages. The apoptosis cell death by pro-apoptotic protein BAX and the expression of VEGF were evaluated using immunohistochemistry. RESULTS: In the bilaterally ovariectomized mice, among the 455 counted normal follicles, a lower rate of primordial and primary follicles and a higher rate of preantral and antral follicles were observed (p = 0.002). However, the percentages of preantral and antral follicles, and the corpus luteum were significantly lower in the intact control group (among the 508 counted normal follicles in this group) compared to other transplanted groups (p = 0.002). The number of BAX-positive cells in all groups was not significantly different. The VEGF expression was prominent in vessels of the corpus luteum, and also in the theca layer of large follicles of studied groups. CONCLUSION: Early discharge of ovarian reserve was prominent in the bilaterally ovariectomized group but the incidence of apoptotic cells and VEGF expression as angiogenic factor did not differ in both ovariectomized mice. Thus, unilaterally ovariectomy has less side effects on the ovarian reserve compared to bilateral ovariectomy.

Chromosomal aberrations in C-arm fluoroscopy, CT-scan, lithotripsy, and digital radiology staff.

We have assessed chromosome-type aberrations and micronuclei in the peripheral lymphocytes of personnel working with C-arm fluoroscopy, multi-slice CT-scan, lithotripsy, and digital radiology medical procedures. The study population comprised of 46 exposed workers and 35 controls matched for age, gender, and other confounding factors. Chromosome-type aberrations and micronuclei were analyzed and compared with occupational dosimetry data. The highest frequency of both chromosome aberrations (1.62 CA/100 cells) and MN (MN = 7.47 ± 2.55) was observed in the operating room group. According to occupational dosimetry, surgeons and medical staff received 0-2.99 mSv over the previous year, well below the limit established by the International Committee on Radiation Protection. An increased level of chromosomal aberrations was observed among workers exposed in the operating rooms. We recommend that operating room radiation safety programs be improved and better supervised, in particular for orthopedic surgeons and personnel performing fluoroscopically guided procedures.

Assessment of ovarian tissues autografted to various body sites followed by IVM in mouse.

BACKGROUND: Ovarian tissue transplantation is emerging technologies for fertility preservation. In addition, in vitro maturation (IVM) of oocytes retrieved from ovarian tissues may overcome the fertility defects in certain cases. OBJECTIVE: The aim was to evaluate the best site for ovarian tissue transplantation in mice. Also, feasibility of IVM of oocytes retrieved from auto grafted ovarian tissues was freshly assessed. MATERIALS AND METHODS: Hemi-ovaries from 6 weeks old mice were auto grafted into kidney capsule (K) versus the back muscle (B) and leg muscle (L) in a mouse auto graft model which was stimulated with gonadotrophins. Then ovarian grafts were recovered and processed histologically for follicle assessment compared with control, also the ability of oocytes to mature with IVM was studied 14 days after transplantation. RESULTS: Total follicle count was significantly higher in K-graft (3.5±3.17) and the antral follicles were only observed in K-site model. The number of retrieved immature oocytes as well as successful IVM in K-grafts was significantly higher than other groups (p=0.008, p=0.016). CONCLUSION: The kidney capsule is a promising site for ovarian tissue auto graft in mice. This resulted in better follicular survival and IVM outcomes.

Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy. MATERIAL AND METHODS: in vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock׳s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10 days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies. RESULTS: in vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves. CONCLUSIONS: in vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration.

Differentiation of bone marrow mesenchymal stem cells into chondrocytes after short term culture in alkaline medium.

BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) are one of the undifferentiated multipotential cell sources of human body. MSCs have the capacity to form a variety of cell types, especially chondrocytes and osteocytes. Learning about responses of MSCs to external milieu and chemical factors such as pH could recommend new approaches for preparation of suitable scaffolds for bone and cartilage tissue engineering. In present study, the effect of alkaline medium on chondrogenic and osteogenic differentiation of rat MSCs was evaluated. METHODS: MSCs were harvested from bone marrow of animals and then the response of passage1 and 2 of MSCs (P1 MSCs & P2 MSCs) to the culture in alkaline medium (pH: 8) was evaluated. Cytochemical and immunocytochemical staining were performed to distinguish chondrocytes and osteocytes. Real-time PCR was performed to evaluate the type II collagen and osteopontin mRNA levels. RESULTS: Staining for type II collagen, a chondrocytic specific marker, revealed that after one-week culture in alkaline medium, a considerable amount of P1 MSCs had shown chondrocytic morphology. By prolonging the culture period up to 4 weeks, osteogenic cells with expanded matrix and mineralized areas around them were appeared. Results of real-time PCR showed that P1 MSCs after one week culture in alkaline medium expressed highest rate of type II collagen and osteopontin mRNA among all groups. CONCLUSION: This study demonstrated that alkaline medium is a potent chondrogenic differentiation inducer for MSCs in their first passage.