Repeated ovarian hyperstimulation promotes depression-like behavior in female mice.

Controlled ovarian hyperstimulation (COH) is a common step for treating infertile couples undergoing assisted reproductive technologies and in female fertility preservation cycles. In some cases, undergoing multiple COHs is required for couples to conceive. Behavioral changes such as anxiety and depression can be caused by ovulation-inducing drugs. Sex steroids play a role in locomotor activity, behavioral changes, and nociception, specifically during fluctuations and sudden drops in estrogen levels. This study evaluated the effect of repeated ovarian hyperstimulation (ROH) on weight, locomotor activity, anxiety-like and depression-like behavior, and nociception in female mice. The animals were divided into two groups: control (placebo; Control) and treated (ROH; Treatment). Ovulation was induced once weekly for 10 consecutive weeks. Locomotor activity (open field test), anxiety-like behavior (elevated plus maze, hole board, and marble burying tests), depression-like behavior (splash and forced swim tests), and nociception (hot plate and Von Frey tests) were evaluated before and after ROH. Statistical analysis was conducted using two-way analysis of variance to evaluate the effects of ROH, age of mice, and their interaction. The results suggested that ROH contributed to weight gain, increased locomotor activity, and induced depression-like behavior in female mice. Furthermore, the age of the mouse contributed to weight gain, increased locomotor activity, and induced anxiety-like and depression-like behavior in female mice. ROH could change the behavior of female mice, particularly inducing depression-like behavior. Further studies are required to evaluate various COH protocols, specifically with drugs that prevent fluctuations and drastic drops in estrogen levels, such as aromatase inhibitors.

Review on the current long-term, limited lead electroencephalograms.

In the last century, 10-20 lead EEG recordings became the gold standard of surface EEG recordings, and the 10-20 system provided comparability between international studies. With the emergence of advanced EEG sensors, that may be able to record and process signals in much more compact units, this additional sensor technology now opens up opportunities to revisit current ambulatory EEG recording practices and specific patient populations, and even electrodes that are embedded into the head surface. Here, we aim to provide an overview of current limited sensor long-term EEG systems. We performed a literature review using Pubmed as a database and included the relevant articles. The review identified several systems for recording long-term ambulatory EEGs. In general, EEGs recorded with these modalities can be acquired in ambulatory and home settings, achieve good sensitivity with low false detection rates, are used for automatic seizure detection as well as seizure forecasting, and are well tolerated by patients, but each of them has advantages and disadvantages. Subcutaneous, subgaleal, and subscalp electrodes are minimally invasive and provide stable signals that can record ultra--long-term EEG and are in general less noisy than scalp EEG, but they have limited spatial coverage and require anesthesia, a surgical procedure and a trained surgeon to be placed. Behind and in the ear electrodes are discrete, unobtrusive with a good sensitivity mainly for temporal seizures but might miss extratemporal seizures, recordings could be obscured by muscle artifacts and bilateral ictal patterns might be difficult to register. Finally, recording systems using electrodes in a headband can be easily and quickly placed by the patient or caregiver, but have less spatial coverage and are more prone to movement because electrodes are not attached. Overall, limited EEG recording systems offer a promising opportunity to potentially record targeted EEG with focused indications for prolonged periods, but further validation work is needed.

Application of multiple validated algorithms for identifying incident breast cancer among individuals with atopic dermatitis.

PURPOSE: Validated algorithms (VAs) in insurance claims databases are often used to estimate the prevalence and incidence of comorbidities and evaluate safety signals. However, although they are then used in different data sources or subpopulations from those in which they were developed the replicability of these VAs are rarely tested, making their application and performance in these settings potentially unknown. This paper describes testing multiple VAs used to identify incident breast cancer cases in a general population and in an indication-specific population, patients with atopic dermatitis (AD). METHODS: Two algorithms were tested in multiple insurance claims databases and four cohorts were created. Modifications were made to account for the US insurance setting. The resulting incidence rates (IRs) were then compared across algorithms and against surveillance, epidemiology, and end results (SEER) estimates to assess reliability. RESULTS: Algorithm 1 produced low IRs compared to Algorithm 2. Algorithm 2 provided similar estimates to those of SEER. Individuals in the AD cohorts experienced lower incident breast cancer cases than those in the general population cohorts. CONCLUSION: Regardless of an algorithm's reported accuracy, the original study setting and targeted population for the VAs may matter when attempting to replicate the algorithm in an indication-specific subpopulation or varying data sources. Investigators should use caution and conduct sensitivity analyses or use multiple algorithms when attempting to calculate incidence or prevalence estimates using VAs.

Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.

BACKGROUND: Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy. METHODS: This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined. RESULTS: A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7-12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024). CONCLUSION: No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.

Pharmacological Potential of cis-jasmone in Adult Zebrafish (Danio rerio).

This study evaluates the pharmacological potential of cis-jasmone (CJ) in adult zebrafish (Danio rerio; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; p. o.) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABAA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABAA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.

Cytotoxicity, antinociceptive and gastroproiltective potential of the Abuta selloana Eichler: a fruit plant from Catarinense flora, Brazil.

This study evaluated some biological activities of extracts from Abuta selloana. The gastroprotective potential was determined against ethanol/HCl- and indomethacin-induced gastric ulcers, whereas the antinociceptive effect was evaluated by acetic acid-induced abdominal contortions in mice. The cytotoxicity activity was measured against human cancer cell lines: U251 (glioma), MCF-7 (breast cancer) and NCI-H460 (lung cancer). The radical scavenger potential was verified; and preliminary phytochemical analyses were performed. The phytochemical screening revealed higher levels of phenolic compounds in all extracts. Moreover, the methanolic extract from pulp fruit (MEPu), peel fruit (MEPe), branches (MEB) and leaves (MEL) scavenged the DPPH radical at 100 µg/mL. Besides, only MEL presented GI50 < 30 µg/mL in all tested cells. Besides, MEPu, MEPe, MEB or MEL at 10 mg/kg (i.p) reduced the abdominal contortions at 47.22%, 63.31%, 84.59% and 37.76%, respectively. The MEPu, MEPe, MEB and MEL reduced the ethanol/HCl- and indomethacin- induced ulcer at 250 mg/kg (p.o). In conclusion, A. selloana had interesting biological activities; presenting the leaves as a promising source for compounds with cytotoxic potential, however, further studies should be performed to confirm its antitumoral activity. Besides, the whole plant can be an important source of bioactive compounds associated with gastroprotective and antinociceptive properties.

Dimethyl Cardamonin from Fruits of Campomanesia reitziana D. Legrand Promotes Gastroprotection and Gastric Healing Effects in Rodents.

Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C. reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C. reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1 mg/kg, i.p. and 1 and 3 mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated in vivo and in vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity in vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.

Parkia platycephala Lectin (PPL) Inhibits Orofacial Nociception Responses via TRPV1 Modulation.

Lectins are a heterogeneous group of proteins that reversibly bind to simple sugars or complex carbohydrates. The plant lectin purified from the seed of Parkia platycephala (PPL) was studied. This study aimed to investigate the possible orofacial antinociceptive of PPL lectin in adult zebrafish and rodents. Acute nociception was induced by cinnamaldehyde (0.66 µg/mL), 0.1% acidified saline, glutamate (12.5 µM) or hypertonic saline (5 M NaCl) applied into the upper lip (5.0 µL) of adult wild zebrafish. Zebrafish were pretreated by intraperitoneal injection (20 µL) with vehicle (Control) or PPL (0.025; 0.05 or 0.1 mg/mL) 30 min before induction. The effect of PPL on zebrafish locomotor behaviour was evaluated in the open field test. Naive groups were included in all tests. In one experiment, animals were pre-treated with capsazepine to investigate the mechanism of antinociception. The involvement of central afferent C-fibres was also investigated. In another experiment, rats pre-treated with PPL or saline were submitted to the temporomandibular joint formalin test. Other groups of rats were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of mechanical sensitivity using von Frey. PPL reduced nociceptive behaviour in adult zebrafish, and this is related to the activation of the TRPV1 channels since antinociception was effectively inhibited by capsazepine and by capsaicin-induced desensitization. PPL reduced nociceptive behaviour associated with temporomandibular joint and neuropathic pain. The results confirm the potential pharmacological relevance of PPL as an inhibitor of orofacial nociception in acute and chronic pain.

Development of a Nanoformulation for Oral Protein Administration: Characterization and Preclinical Orofacial Antinociceptive Effect.

Nanoencapsulation is a valid alternative for the oral administration of peptide drugs and proteins, as nanoparticles protect them from proteolytic degradation in the gastrointestinal tract and promote the absorption of these macromolecules. The orofacial antinociceptive effect of frutalin (FTL), through the intraperitoneal route, has already been proven. This study aimed to develop, characterize, and evaluate the orofacial antinociceptive activity of an oral formulation containing FTL in acute and neuropathic preclinical tests. Nanoencapsulated FTL was administered by oral route. The acute nociceptive behavior was induced by administering capsaicin to the upper lip and NaCl to the right cornea. The nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The neuropathic pain model involved infraorbital nerve transection (IONX), which induced mechanical hypersensitivity and was assessed by von Frey stimulation. Trpv1 gene expression was analyzed in the trigeminal ganglion. The analyzed sample did not show any cytotoxicity; 52.2% of the FTL was encapsulated, and the size of the nanocapsule was less than 200 nm, the polydispersion was 0.361, and the zeta potential was - 5.87 and - 12.8 mV, with and without FTL, respectively. Nanoencapsulated FTL administered by oral route had an orofacial antinociceptive effect in acute and neuropathic rodent models. The antinociceptive effect of FTL was prevented by ruthenium red, but not by camphor. FTL reduced Trpv1 gene expression. FTL promotes orofacial antinociception, probably due to the antagonism of TRPV1 channels, and the nanoformulation represents an effective method for the oral administration of this protein. HIGHLIGHTS: • Nanoformulation for oral protein administration. • Nanocapsule containing FTL prevents orofacial nociceptive acute and neuropathic pain. • Frutalin promotes orofacial antinociception behavior antagonism of TRPV1 channels.

Phaseolus vulgaris L. Leaves Increase Short-Chain Fatty Acid (SCFA) Production, Ameliorating Early Metabolic Alterations.

High-fat/high-fructose diets promote early metabolic disorders in weight and lipid and glucose metabolism. Bioactive compounds such as polyphenols and fiber present in plant-based food prevent the development of metabolic disorders. The objective of the present study was to evaluate the effect of Phaseolus vulgaris L. Flor de Mayo Eugenia (FME) bean leaves on early metabolic alterations in male Wistar rats fed a high-fat/high-fructose diet. After proximate and chemical analysis of FME bean leaves, thirty-six male Wistar rats (ethical approval 06FCN2019 and 77FCN2019) were randomly assigned to one of four groups: 1) standard diet (S) fed with Rodent Laboratory Chow 5001®; 2) standard diet + 10% dry FME bean leaves (SBL); 3) high-fat (lard) and high-fructose diet (H); and 4) high-fat/high-fructose diet + 10% dry FME bean leaves (HBL). The study was carried out for six weeks. Group H exhibited early metabolic alterations compared to Group S: final weight gain (↑15%), abdominal fat accumulation (waist circumference, ↑11%), triglycerides (↑30%), glucose (↑16%), insulin resistance (HOMA-IR, ↑32%), and fecal triglycerides (↑284%) and decreased total short-chain fatty acids (SCFAs, ↓17%). FME bean leave supplementation (HBL) prevented body weight gain (↓12%), abdominal fat accumulation (waist circumference, ↓10%), and early insulin resistance (glucose area under the curve, ↓6%) compared to Group H. The supplementary bean leave diet increased SCFA production (↑54%), most likely mediated by the fiber and polyphenols present in the leaves. Therefore, bean leaves are a low-cost alternative for human nutritional care and prevention of early metabolic alterations.

Open versus minimally invasive total gastrectomy after neoadjuvant chemotherapy: results of a European randomized trial.

BACKGROUND: Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated. METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival. RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery. CONCLUSION: These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.

Effect of altitude on COVID-19 mortality in Ecuador: an ecological study.

BACKGROUND: The SARS-CoV-2/COVID-19 pandemic has claimed nearly 900,000 lives worldwide and infected more than 27 million people. Researchers worldwide are studying ways to decrease SARS-CoV-2 transmission and COVID-19 related deaths. Several studies found altitude having a negative association with both COVID-19 incidence and deaths. Ecuadorian data was used to explore the relationship between altitude and COVID-19. METHODS: This is an ecological study examining province-level data. To explore a relationship between altitude and COVID-19, this study utilized publicly available COVID-19 data and population statistics. ANOVA, correlation statistics, and a multivariate linear model explored the relationship between different Ecuadorian altitudes against incidence, mortality, and case-fatality rates. Population statistics attributed to COVID-19 were included in the linear model to control for confounding factors. RESULTS: Statistically significant differences were observed in the regions of Amazónica, Sierra, Costa of Ecuador for incidence, mortality, and case fatality rates, suggesting an association between altitude and SARS-CoV-2 transmission and COVID-19 disease severity (p-value ≤0.05). In univariate analysis, altitude had a negative association to mortality rate with a 1-unit change in altitude resulting in the decrease of 0.006 units in mortality rate (p-value = 0.03). The multiple linear models adjusted for population statistics showed a statistically significant negative association of altitude with mortality rate (p-value = 0.01) with a 1-unit change in altitude resulting in the decrease in mortality rate by 0.015 units. Overall, the model helped in explaining 50% (R2 = 0.4962) of the variance in mortality rate. CONCLUSION: Altitude may have an effect on COVID-19 mortality rates. However, based on our model and R2 value, the relationship between our variables of interest and COVID-19 mortality may be nonlinear. More research is needed to understand why altitude may have a protective effect against COVID-19 mortality and how this may be applicable in a clinical setting.

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.

BACKGROUND: Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. METHODS: We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). RESULTS: The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. CONCLUSIONS: In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).

Antinociceptive activity of 3ß-6ß-16ß-trihydroxylup-20 (29)-ene triterpene isolated from Combretum leprosum leaves in adult zebrafish (Danio rerio).

Drugs used to treat pain are associated with adverse effects, increasing the search for new drugs as an alternative treatment for pain. Therefore, we evaluated the antinociceptive behavior and possible neuromodulation mechanisms of triterpene 3ß, 6ß, 16ß-trihydroxylup-20(29)-ene (CLF-1) isolated from Combretum leprosum leaves in zebrafish. Zebrafish (n = 6/group) were pretreated with CLF-1 (0.1 or 0.3 or 1.0 mg/mL; i.p.) and underwent nociception behavior tests. The antinociceptive effect of CFL-1 was tested for modulation by opioid (naloxone), nitrergic (L-NAME), nitric oxide and guanylate cyclase synthesis inhibitor (methylene blue), NMDA (Ketamine), TRPV1 (ruthenium red), TRPA1 (camphor), or ASIC (amiloride) antagonists. The corneal antinociceptive effect of CFL-1 was tested for modulation by TRPV1 (capsazepine). The effect of CFL-1 on zebrafish locomotor behavior was evaluated with the open field test. The acute toxicity study was conducted. CLF-1 reduced nociceptive behavior and corneal in zebrafish without mortalities and without altering the animals' locomotion. Thus, CFL-1 presenting pharmacological potential for the treatment of acute pain and corneal pain, and this effect is modulated by the opioids, nitrergic system, NMDA receptors and TRP and ASIC channels.

Anxiolytic-like effect of chalcone N-{4'[(2E)-3-(3-nitrophenyl)-1-(phenyl)prop-2-en-1-one]} acetamide on adult zebrafish (Danio rerio): Involvement of the 5-HT system.

The action of anxiolytic compounds that act on selective serotonin receptors (SSRIs) have been scarcely evaluated. Serotonergic drugs have been shown to be effective in treating anxiety without presenting adverse effects as benzodiazepines. However, the anxiolytic effects take days to occur. This study aimed to evaluate the anxiolytic effect of the synthetic chalcone, 4'-[(2E) -3- (3-nitrophenyl) -1- (phenyl) prop-2-en-1-one] acetamide (PAAMNBA), and its possible mechanism of action in adult zebrafish (Danio rerio). PAAMNBA was synthesized with a yield of 51.3% and its chemical structure was determined by 1H and 13C NMR. Initially, PAAPMNBA was intraperitoneally administered to zebrafish (n = 6/group) at doses of 4, 12, or 40 mg/kg, and the animals were subsequently subjected to acute and open field toxicity tests. PAAMNBA was administered to the other groups (n = 6/group) for analyzing its effect in the light and dark test. The involvement of the serotonergic (5HT) system was also evaluated using 5-HTR 1, 5-HTR 2A/2C, and 5-HTR 3A/3B receptor antagonists, namely, pizotifeo, granizetron, and ciproeptadina, respectively. Molecular coupling was performed using the 5-HT1 receptor. PAAMNBA was found to be non-toxic, reduced the locomotor activity, and had an anxiolytic effect in adult zebrafish. The effect was reduced by pretreatment with pizotifene and was not reversed by treatment with granizetron and cyproeptadine. A previous in vivo molecular coupling study indicated that chalcones interact with the 5-HT1 receptor. The results suggested that the chalcone, PAAPMNBA, has anxiolytic activity, that is mediated by the serotonergic system via the 5-HT1 receptor. The interaction of PAAPMNBA with the 5-HT1 receptor was confirmed by molecular docking studies.

Xanthones and Cancer: from Natural Sources to Mechanisms of Action.

Xanthones are a class of heterocyclic natural products that have been widely studied for their pharmacological potential. In fact, they have been serving as scaffolds for the design of derivatives focusing on drug development. One of the main study targets of xanthones is their anticancer activity. Several compounds belonging to this class have already demonstrated cytotoxic and antitumor effects, making it a promising group for further exploration. This review therefore focuses on recently published studies, emphasizing their natural and synthetic sources and describing the main mechanisms of action responsible for the anticancer effect of promising xanthones.

Management of gastrocutaneous fistulas following gastrostomy: surgery as a therapeutic option.

Gastrocutaneous fistulas (GCF) following removal of gastrostomy tubes are an uncommon complication with many therapeutic options. It is a drawback that concerns both patient and surgeon, hindering the decision to perform an invasive treatment. Despite emerging minimally invasive procedures, we must not forget that surgery continues to be the standard treatment when they all fail.

The role of percutaneous endoscopic gastrostomy in the treatment of acute gastric volvulus.

Gastric volvulus is an uncommon pathology that can occur acutely, in a chronic setting, or even as a casual finding. The primary kind occurs in 30% of patients. Secondary causes include hiatal hernia types II-III up to 70% of cases. The main treatment of acute gastric volvulus is gastric decompression, by means of a nasogastric tube (NGT) or endoscopy. However, it is not a procedure exempt from complications. Traditionally, definitive treatment involves surgery, consisting in hernia reduction with gastropexy/anti-reflux technique and/or hiatoplasty. We present the case of a 83-year-old woman with permanent atrial fibrillation, among other cardiovascular conditions.

Transitory response of a myelodysplastic syndrome with deletion of chromosome 5q to thalidomide. Report of one case.

Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.

Late-Onset Hematological Toxicity (LOHT) in Patients with B-Cell Lymphomas: A Survey in 758 Cases.

BACKGROUND: The increasing survival of patients with non-Hodgkin lymphoma has allowed the diagnosis of long-term com- plications, including late-onset hematological toxicity (LOHT), transitory cytopenias, or therapy-related myeloid neoplasm (t-MDS/t-AML). OBJECTIVE: The objective of the study was to determine the frequency and clinical evolution of LOHT in patients with lymphoproliferative malignancies. MATERIALS AND METHODS: Two cohorts of patients B-cell lymphomas were reviewed. Patients who achieved full hematologic recovery at the end of treatment, and thereafter developed any degree of cytopenia were included in the study. Clinical and biochemical parameters were compared between patients with and without cytopenias with X2 test. Bi-and multivariate analyses were performed to evaluate factors associated with the development of late-onset cytopenias. RESULTS: Of 758 patients enrolled, 19 developed cytopenias (2.5%). Transitory cytopenia was documented in 6 cases, 3 developed ICUS, 8 t-MDS, and 2 t-AML. In patients with FL, only hemoglobin < 12 g/dL (p = 0.032) and >6 nodal areas (p = 0.037) at diagnosis were factors statistically significant for the development of cytopenia. During cytopenias, 55% of patients died. CONCLUSIONS: LOHT constitutes a cause of morbidity and mortality in 2.5% of lymphoma patients treated with different therapy regimens.