Diastereoselective and Scalable Synthesis of 6-(S)-Hydroxycannabidivarin.

The synthesis of 6-(S)-hydroxycannabidivarin was required to assess its biological activity in the treatment of neurological disorders. A novel and scalable synthesis has been developed where the key step involves a Friedel-Crafts alkylation of phloroglucinol with (1S,2R,5R)-2-hydroxy-2-methyl-5-(prop-1-en-2-yl)cyclohex-3-en-1-ylbenzoate. Careful optimization of the reaction conditions identified trifluoromethanesulfonic acid in isopropyl acetate as the best catalyst/solvent combination, providing optimum regioselectivity, diastereoselectivity, and yield for this step. This enabled the multigram synthesis of 6-(S)-hydroxycannabidivarin in 10 steps from S-(+)-carvone.

Post-traumatic avascular necrosis of the talus.

In this comprehensive case report, we examine a 29-year-old male who suffered a high-energy vehicular accident, resulting in a type III Hawkins fracture of the talus. This specific fracture type is critically associated with a greater than 90% risk of progressing to avascular necrosis (AVN) of the talus, a severe and debilitating condition. Alongside this, the patient sustained fractures of the medial and lateral malleolus. Due to extensive swelling and severe circulatory disorders, an immediate emergency surgical procedure was necessitated, employing nail fixation as a stabilizing intervention. Over the course of 12 months following the surgery, despite routine post-operative imaging including X-rays and computed tomography (CT) scans, the patient continued to experience significant pain and impairment. This condition led to further investigations, culminating in a magnetic resonance imaging (MRI) that revealed an area of 19.8∕20.9 mm of AVN on the talus dome's upper-lateral facet. Interestingly, earlier CT scans had indicated multiple osteitic lesions, but these findings lacked a clear clinical correspondence, presenting a diagnostic challenge. To resolve this ambiguity and to definitively distinguish between necrosis and infection, a targeted histopathological analysis was deemed necessary. This analysis was conducted on a bone fragment extracted during a follow-up surgical procedure for nail removal. The results from this analysis present an area of bone and myeloid tissue necrosis unequivocally confirming the presence of AVN, effectively ruling out osteitis as a potential diagnosis. This critical diagnostic clarification allowed for a shift in therapeutic strategy, enabling the initiation of a more focused and potentially curative treatment regimen.

Ultrasonographic Algorithm for the Assessment of Sentinel Lymph Nodes That Drain the Mammary Carcinomas in Female Dogs.

The status of sentinel lymph nodes (SLNs) is decisive in staging, prognosis, and therapeutic approach. Using an ultrasonographic examination algorithm composed of B-mode, Doppler technique, contrast-enhanced ultrasound (CEUS) and elastography, this study aimed to determine the diagnostic performance of the four techniques compared to histopathological examination. 96 SLNs belonging to 71 female dogs with mammary gland carcinomas were examined. After examinations, mastectomy and lymphadenectomy were performed. Histopathological examination confirmed the presence of metastases in 54 SLNs. The elasticity score had the highest accuracy-89.71%, identifying metastases in SLNs with 88.9.9% sensitivity (SE) and 90.5% specificity (SP), ROC analysis providing excellent results. The S/L (short axis/long axis) ratio showed 83.3% SE and 78.6% SP as a predictor of the presence of metastases in SLN having a good accuracy of 81.2%. On Doppler examination, the resistivity index(RI) showed good accuracy of 80% in characterizing lymph nodes with metastases versus unaffected ones; the same results being obtained by CEUS examination. By assigning to each ultrasonographic parameter a score (0 or 1) and summing up the scores of the four techniques, we obtained the best diagnostic performance in identifying lymph node metastases with 92.2% accuracy. In conclusion, the use of the presented algorithm provides the best identification of metastases in SLNs, helping in mammary carcinoma staging and appropriate therapeutic management.

Genetic depletion of 5-HT increases central apnea frequency and duration and dampens arousal but does not impact the circadian modulation of these variables.

We examined the impact of serotonin (5-HT) on the frequency and duration of central apneic events and the frequency of accompanying arousals during nonrapid and rapid eye movement (NREM and REM, respectively) sleep across the light/dark cycle. Electroencephalography, electromyography, core body temperature, and activity were recorded for 24 h following implantation of telemeters in wild-type (Tph2+/+) and tryptophan hydroxylase 2 knockout (Tph2-/-) male mice. The frequency and duration of central apneic events were increased, the number of apneic events coupled to an arousal was decreased, and the ventilatory sensitivity to hypoxia and hypercapnia was decreased in the Tph2-/- compared with the Tph2+/+ mice during NREM sleep. Apnea frequency and duration were similar in the Tph2-/- and Tph2+/+ mice during REM sleep. The duration of apneic events during REM compared with NREM sleep was similar in the Tph2-/- mice. In contrast, the duration was greater during REM sleep in the Tph2+/+ mice. Our results also revealed that apnea frequency was greater during the light compared with the dark cycle. Circadian modulation of this variable was evident in both the Tph2-/- and Tph2+/+ mice during NREM and REM sleep. We conclude that depletion of 5-HT increases the frequency and duration of central apneic events, dampens arousal, and blunts the ventilatory response to hypoxia and hypercapnia during NREM sleep but is not essential for the circadian modulation of these variables. NEW & NOTEWORTHY The presence of serotonin (5-HT) in the central nervous system diminishes the frequency of central apneic events. This neuromodulator also moderates the duration of central apneic events and promotes arousal from central events if they occur during nonrapid eye movement (NREM) sleep. However, 5-HT is not responsible for the circadian modulation of apnea frequency, which we found was greater during NREM sleep in the light compared with the dark cycle.