Preclinical activity of melflufen (J1) in ovarian cancer

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration

Changes in Grauer's gorilla (Gorilla beringei graueri) and other primate populations in the Kahuzi-Biega National Park and Oku Community Reserve, the heart of Grauer's gorilla global range

Grauer's gorillas (Gorilla beringei graueri) have declined drastically across their range in eastern Democratic Republic of Congo (DRC). Survey data analysed in 2016 estimated a 77% decline in numbers between the mid- 1990s and 2016 and predicted that Kahuzi-Biega National Park (KBNP), and the contiguous Oku Community Reserve (OCR) held much of the global population. An estimate of 3800 Grauer's gorillas was made across its range at that time. Here, we publish the most extensive survey of Grauer's gorilla numbers to date, using nest counts from 230 line transects across KBNP and OCR to derive more accurate estimates of both gorilla and chimpanzee numbers. Gorilla numbers were estimated from line transects at 1,571 (95% confidence interval [CI]: 824–2,993) within KBNP and at 2,244 (95% CI: 1,471–3,422) in OCR. Eastern chimpanzee (Pan troglodytes schweinfurthii) numbers were estimated at 2,500 (95% CI: 1,804–3,462) in KBNP and 687 (95% CI: 472–999) in OCR. Estimates of total numbers for the survey area were 5,252 (95% CI: 3,687–7,481) Grauer's gorillas and 4,275 (95% CI: 3,322–5,502) eastern chimpanzees. Chimpanzee numbers were not significantly different from the estimates in the mid-1990s but the gorillas had significantly declined, mostly in KBNP. Modeled densities of these apes indicated that distances to mines, villages, or roads significantly explained part of the distribution of these apes, with higher densities also found in more rugged and remote sites. Other primates have all declined in this region, likely due to bushmeat hunting, especially the Endangered Ulindi River Red Colobus Piliocolobus lulindicus. These results confirm the negative impact of insecurity on Grauer's gorilla but indicate that the population declines may not be as great as previously feared. Using our revised gorilla density estimate we revise the original estimate of global numbers from 3,800 to 6,800 individuals

Social Perceptions of Forest Ecosystem Services in the Democratic Republic of Congo

The forests of the Albertine Rift are known for their high biodiversity and the important ecosystem services they provide to millions of inhabitants. However, their conservation and the maintenance of ecosystem service delivery is a challenge, particularly in the Democratic Republic of the Congo. Our research investigates how livelihood strategy and ethnicity affects local perceptions of forest ecosystem services. We collected data through 25 focus-group discussions in villages from distinct ethnic groups, including farmers (Tembo, Shi, and Nyindu) and hunter-gatherers (Twa). Twa identify more food-provisioning services and rank bush meat and honey as the most important. They also show stronger place attachment to the forest than the farmers, who value other ecosystem services, but all rank microclimate regulation as the most important. Our findings help assess ecosystem services trade-offs, highlight the important impacts of restricted access to forests resources for Twa, and point to the need for developing alternative livelihood strategies for these communities

Acta Psychiatr Scand

INTRODUCTION: Depression is one of the most common co-morbidities during pregnancy; with severe symptoms, antidepressants are sometimes recommended. Social determinants are often linked with antidepressant use in the general population, and it is not known if this is the case for pregnant populations. Our objective was to determine if social determinants are associated with prenatal antidepressant intake via a systematic review and meta-analysis. METHODS: A systematic search of five databases was conducted to identify publications from inception to October 2022 that reported associations with prenatal antidepressant intake (use/continuation) and one or more social determinants: education, race, immigration status, relationship, income, or employment. Eligible studies were included in random effects meta-analyses. RESULTS: A total of 23 articles describing 22 studies were included. Education was significantly and positively associated with prenatal antidepressant continuation and heterogeneity was moderate. (Odds ratio = 0.83; 95% CI, 0.78 to 0.89; p < 0.00001; I(2)  = 53%). Meta-analyses of antidepressant use and education, race, and relationship status, and antidepressant continuation and income were not significant with high levels of heterogeneity. DISCUSSION: While most social determinants in this review were not linked with prenatal antidepressant intake, lower maternal education level does seem to be associated with lower rates of prenatal antidepressant continuation. CONCLUSIONS: Education appears to be linked with prenatal antidepressant intake. The low number of included studies precludes conclusive evidence for other social determinants.Troubles de l'humeur et de l'anxiété maternelles prénatales et leur traitement, impact sur le développement de l'enfan