Early treatment with JNJ-46356479, a mGluR2 modulator, improves behavioral and neuropathological deficits in a postnatal ketamine mouse model of schizophrenia.

Positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), may mitigate the glutamate storm during the early stages of schizophrenia (SZ), which could be especially useful in the treatment of cognitive and negative symptoms. We evaluated the efficacy of early treatment with JNJ or clozapine (CLZ) in reversing behavioral and neuropathological deficits induced in a postnatal ketamine (KET) mouse model of SZ. Mice exposed to KET (30 mg/kg) on postnatal days (PND) 7, 9, and 11 received JNJ or CLZ (10 mg/kg) daily in the adolescent period (PND 35-60). Mice exposed to KET did not show the expected preference for a novel object or for social novelty, but they recovered this preference with JNJ treatment. Similarly, KET group did not show the expected dishabituation in the fifth trial, but mice treated with JNJ or CLZ recovered an interest in the novel animal. Neuronal immunoreactivity also differed between treatment groups with mice exposed to KET showing a reduction in parvalbumin positive cells in the prefrontal cortex and decreased c-Fos expression in the hippocampus, which was normalized with the pharmacological treatment. JNJ-46356479 treatment in early stages may help improve the cognitive and negative symptoms, as well as certain neuropathological deficits, and may even obtain a better response than CLZ treatment. This may have relevant clinical translational applications since early treatment with mGluR2 modulators that inhibit glutamate release at the onset of critical phases of SZ may prevent or slow down the clinical deterioration of the disease.

COVID-19 inpatients with psychiatric disorders: Real-world clinical recommendations from an expert team in consultation-liaison psychiatry.

BACKGROUND: The management of coronavirus disease 2019 (COVID-19) in patients with comorbid psychiatric disorders poses several challenges, especially regarding drug interactions. METHODS: We report three representative case-scenarios on patients with psychiatric disorders and COVID-19 to provide a practical approach based on the existing literature and the clinical experience of an expert team in consultation-liaison psychiatry. CASE-CENTERED RECOMMENDATIONS: Psychopharmacological ongoing treatments should be prioritized and most doses should be reduced 25-50% of original dose if the patient receives lopinavir/ritonavir, with some exceptions including quetiapine, asenapine, olanzapine, sertraline, lamotrigine, bupropion, and methadone. If the psychopharmacological usual doses are in the low-to-median range levels, a dose change during COVID-19 drugs co-administration is not recommended, but only ECG and clinical monitoring of adverse effects and drug levels if required. Furthermore, when introducing a psychopharmacological drug, dose titration should be progressive, with ECG monitoring if cardiotoxic interactions are present. (A) In agitated delirium, olanzapine is recommended as first-line antipsychotic and quetiapine should be avoided. (B) In severe mental illness (SMI), essential treatments should be maintained. (C) In non-SMI with depressive/anxiety symptoms, psychological support should be provided and symptoms identified and treated. LIMITATIONS: Most recommendations on pharmacological interactions provide only a limited qualitative approach and quantitative recommendations are lacking. CONCLUSIONS: Patients with psychiatric disorders and COVID-19 should be managed on a personalized basis considering several clinical criteria and, should not be excluded from receiving COVID-19 treatments. Risks of pharmacological interaction are not absolute and should be contextualized, and most psychopharmacological treatments should include an ECG with special attention to QTc interval.

Cannabis use the week before admission to psychiatric in-patient service as a marker of severity.

OBJECTIVE: To evaluate if cannabis dose recorded as standard joint unit (SJU) consumed before admission and other related factors have an influence on psychiatric inpatient's symptom severity and clinical outcomes. METHODS: Cross-sectional study in an acute psychiatric inpatient unit including 106 individuals. Quantity of cannabis was measured as SJU and symptoms severity through the Brief Psychiatric Rating Scale (BPRS). Secondary outcomes (e.g. length of stay) were also assessed. Bivariate analyses and multivariate analyses were performed to determine the effect of SJU consumed before admission on measures of clinical severity. RESULTS: Point prevalence of cannabis use before admission was 25.5%. Mean BPRS score was 55.8 (SD = 16.1); and 62.9 (SD = 11.1) among cannabis users. A low degree positive correlation between SJU consumed the week before admission and BPRS score (rs = 0.28, p = 0.03) was found. In the multivariate analyses both main diagnostic group, Schizophrenia and other psychotic disorders vs. others (Bipolar and Unipolar Affective Disorders and Addictive disorders) (B = 8.327; 95% CI 4.976-11.677) and need of PRN ("pre re nata" or when necessary) administration of antipsychotics and benzodiazepines (B = 12.13; 95% CI 6.868-17.393) were significant predictors, both increasing BPRS score. CONCLUSIONS: The study did not find a correlation between SJU consumed last week and psychiatric severity. On the other hand, individuals with psychotic disorders reported a higher prevalence of cannabis use the week before admission and displayed higher BPRS scores, which points to the need for the development of tailored interventions for high-risk groups. The SJU is a useful quantification tool suitable for further clinical research.

Quality of life, anxiety and depression of German, Italian and French couples undergoing cross-border oocyte donation in Spain.

STUDY QUESTION: What is the quality of life (QoL) and mental health of infertile heterosexual couples from different nations (Italy, Germany and France) undergoing cross-border oocyte donation (OD) in Spain? SUMMARY ANSWER: Women have lower QoL and more anxiety than their male partners; overall French couples have lower QoL than their Italian and German counterparts. WHAT IS KNOWN ALREADY: In Europe, thousands of couples move across national borders annually to seek ARTs, primarily OD, driven mainly by legal restrictions in their countries of origin. Most research shows that infertility and ARTs affect patients' mental health and QoL. The decision to undergo reproductive care abroad might add further emotional and practical complexity. Reliable information on how this experience affects the mental health and QoL of cross-border reproductive care (CBRC) patients is lacking. Moreover, most research has focused on women, and further research on male partners and intercultural differences is needed. STUDY DESIGN, SIZE, DURATION: Cross-sectional study including 548 heterosexual individuals (347 women, 201 men) from Italy, Germany and France seeking IVF with donated oocytes in Barcelona, Spain between March and November 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 432 couples were invited to participate and handed a questionnaire set. Questionnaires were answered separately and anonymously by each member of the couple on the day of embryo transfer. The questionnaire set included the Fertility Quality of Life (FertiQoL) instrument, the generic Hospital Anxiety and Depression Scale (HADS) instrument and three close-ended questions assessing perceived usefulness, desire, and use of psychological support. The overall response rate was 63.4%. MAIN RESULTS AND THE ROLE OF CHANCE: Men reported significantly higher scores than women in the emotional (+13.74; P < 0.001), mind-body (+13.39; P < 0.001) and social (+4.11; P < 0.01) FertiQoL domains, at multilevel analysis controlled for confounder factors. Intercultural differences in QoL of couples were seen. French individuals had significantly lower emotional (-6.44; P < 0.01), mind-body (-7.41; P < 0.001) and relational scores (-6.41; P < 0.001) compared to Italians. Germans showed higher social scores (+6.41; P < 0.001) but lower relational scores (-8.94; P < 0.002) than Italians. Men reported significantly lower anxiety scores for the HADS than their partners (-1.38; P < 0.001), and German couples reported lower anxiety (-1.70; P = 0.003) and depression than their Italian counterparts (-1.56; P < 0.001). French patients were more likely to have required support by a mental health professional due to fertility problems in the past (+0.19; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The scope of this study is limited to heterosexual couples undergoing cross-border OD. Caution on the interpretation of the results in men is advised, mainly because only three men for every five women completed the questionnaire. WIDER IMPLICATIONS OF THE FINDINGS: These findings call for further work to identify the true nature of the differences in QoL and mental health observed. STUDY FUNDING/COMPETING INTEREST(S): None.

Análisis de la evidencia disponible para el consumo de edulcorantes no calóricos. Documento de expertos / Analysis of the available evidence for the intake of non-caloric sweeteners. Expert document

Resumen Los edulcorantes no calóricos representan una buena alternativa para sustituir los sabores dulces sin la respuesta fisiológica que genera el consumo de azúcares. Por sí solos no son herramientas para el control de peso. Su consumo debe ir acompañado de una dieta correcta y un estilo de vida saludable que incluya actividad física. Su utilidad radica en proporcionar el agradable sabor dulce sin el aporte energético. La inocuidad de cada uno de los compuestos aprobados está comprobada y se reevalúa constantemente para tomar en cuenta los resultados de nuevos estudios. Debido a que no existe un edulcorante perfecto, la variedad ayuda a que se desarrollen productos cada vez más agradables para el consumidor. Este trabajo es fruto de una revisión exhaustiva de la bibliografía y de las discusiones de un panel de expertos de diversas especialidades: toxicología, ginecoobstetricia, pediatría, endocrinología, nutrición, medicina interna, salud pública y medicina preventiva, en el que se analizó extensamente la bibliografía se revisó una variedad de trabajos científicos que responden a las interrogantes que habitualmente se hacen los profesionales de la salud acerca de seguridad en diferentes grupos etáreos y con afecciones específicas, ingestión diaria admisible, etc.

Abstract Non-caloric sweeteners are a good alternative to replace the sweet flavors without the physiological response generated by the consumption of sugars. Alone they are not tools for weight control. Its intake must be accompanied by a proper diet and a healthy lifestyle that includes physical activity. Its usefulness lies in providing a pleasant sweet taste without the energy intake. The safety of each of the compounds is tested and approved and constantly reassessed to take into account the results of new studies. Since there is no perfect sweetener, variety helps that more and more pleasing to the consumer products are developed. This work is the result of a comprehensive review of the literature and discussions of a panel of experts from various specialties: toxicology, obstetrics and gynecology, pediatrics, endocrinology, nutrition, internal medicine, public health and preventive medicine, where literature was widely analyzed reviewing a variety of scientific papers that address the questions that usually are made by health professionals on safety in different age groups and with specific diseases, acceptable daily intake, etc.

Endometrial preparation: effect of estrogen dose and administration route on reproductive outcomes in oocyte donation cycles with fresh embryo transfer.

STUDY QUESTION: Is there a difference in live birth rates following endometrial preparation with either a constant or increasing estrogen dose in fresh embryo transfer from oocyte donation cycles? SUMMARY ANSWER: There is no difference in live birth rates between a constant dose versus an increasing dose of estrogen after fresh embryo transfer in oocyte donation cycles with oral or transdermal supplementation. WHAT IS KNOWN ALREADY: Endometrial preparation (EP) with estrogen and progesterone, and embryo-endometrial synchronicity are determinant for adequate embryo implantation. Estrogen is crucial and different exogenous administration patterns could imply variations on EP. Moreover, estrogen undergoes metabolization by the intestines and liver when administered orally, an effect that is bypassed by transdermal administration. Information on the effect of replacement patterns and route of administration of E on reproductive outcomes of women undergoing fresh embryo transfer from oocyte donation cycles is scarce. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study including 8362 embryo transfers following ICSI, corresponding to 8254 patients, between October 2010 and March 2015. A total of 5593 (66.9%) patients received an increasing E dose (ID) (oral: 2 mg/day day(d)1-7, 4 mg days d8-12, 6 mg d13-embryo transfer; transdermal: 75 µg/3 days on d1-6, 150 µg/3 days d7-embryo transfer) while 2769 (33.1%) received a constant dose (CD) of estrogen (oral: 6 mg/day 1-embryo transfer; transdermal: 150 µg/3 days d1-embryo transfer). Embryos were generated by ICSI with fresh or vitrified donor oocytes fertilized with either fresh or frozen sperm from either the couple partner or donor. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort allocation was not related to patient characteristics; instead it reflected an internal policy change in E administration. Effect of estrogen dose (ID versus CD) on biochemical, clinical, ongoing and live birth rates, stratified by administration route, was analyzed by univariate and multivariate analysis adjusted by donor and recipient demographic and cycle characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: No difference in live birth rate was found between CD and ID for oral (33.0 versus 32.5%, P = 0.81) and transdermal (35.3 versus 33.5%, P = 0.33) supplementation. Biochemical pregnancy rate was higher in CD than ID (53.7 versus 47.5%, P < 0.001) when patients received oral supplementation. Adjusted analysis confirmed that oral administration had a greater impact on biochemical pregnancy rates than transdermal (odds ratio (OR) 1.28; 95% confidence interval (CI) 1.11-1.48, P = 0.001 versus OR 1.13; 95% CI 1.00-1.30, P = 0.055). Sub-analysis of transfers between day 12 and 15 of estrogen supplementation showed no difference between CD and ID in pregnancy outcomes. Demographic variables and cycle characteristics were comparable between both groups. Moreover, the use of the oocyte donation model reduces confounding factors related to oocyte age, embryo aneuploidy, and embryo quality. LIMITATIONS, REASONS FOR CAUTION: The greatest limitation of this study is its retrospective nature. On the other hand, this study was performed using donated oocytes; although this is unlikely to affect the results, we cannot exclude the possibility that a high quality female gamete responds differently to endometrial state in comparison to a patient's own oocytes. WIDER IMPLICATIONS OF THE FINDINGS: In fresh embryo transfer from oocyte donation cycles, changes in the protocol of E replacement do not seem to have an impact on clinical outcomes and performance; for this reason estrogen replacement protocols can be adjusted to the patient's characteristics and preferences as well as to the most cost effective strategy. STUDY FUNDING/COMPETING INTERESTS: None.

Fine needle aspiration of breast myofibroblastoma. A case report.

BACKGROUND: The use of fine needle aspiration cytology (FNAC) for the diagnosis of breast diseases in men has received little attention. We report the cytologic and histologic findings of myofibroblastoma of the breast in a 52-year-old man. CASE: Smears disclosed irregular and cohesive sheets of cells, with ill-defined cytoplasm and oval nuclei containing single nucleoli. The nuclear membrane was frequently grooved, and occasional intranuclear cytoplasmic inclusions (pseudoinclusions) were also found. The background was clean and contained scarce collagenous stroma and fragments of myxoid material. To the best of our knowledge, there have been only seven previous reports of breast myofibroblastoma in which the cytologic features are well documented, and none of them mention the presence of pseudoinclusions. CONCLUSION: FNAC could suggest the diagnosis of this distinctly uncommon tumor if evaluated together with the clinical and radiologic findings.

Small cell carcinoma of the kidney: a case report and review of the literature.

Small cell carcinoma is a malignant tumor composed of small cells with a diffuse growth pattern. It has immunohistochemical and ultrastructural features of both neuroendocrine and epithelial neoplasms. These tumors constitute 10% to 20% of malignant tumors in the lung, which is their most frequent site. They have been described in other extrapulmonary sites, where they are defined using the same criteria as used in the lung. These tumors are rarely found in the genitourinary tract. Fewer than 30 cases have been reported in the kidney. The differential diagnosis mainly includes other small round cell tumors and metastatic small cell lung carcinoma. We present and discuss a primary small cell carcinoma of the kidney (to our knowledge the 9th to be reported in the literature), which we studied with light microscopy, immunohistochemistry, electron microscopy, and, for the first time, flow cytometry.

B cell non-Hodgkin's lymphoma in a girl with the DiGeorge anomaly.

The DiGeorge anomaly (DGA) is occasionally associated with cellular immunodeficiency. We report a female infant diagnosed with complete DGA, who developed fatal, high grade, non-Hodgkin's lymphoma that expressed Epstein-Barr virus (EBV). Non-Hodgkin's lymphoma should be considered in children with DGA.

[Heterotopic brain tissue in the pharynx]. / Tejido cerebral heterotópico en la faringe.

The presence of heterotopic brain tissue in the head and neck region is exceptional. Most reported cases have been observed in the nasal region and are called nasal gliomas. The case of a 10-month-old boy with heterotopic brain tissue on the soft palate and nasopharynx is reported. Surgical treatment was successful and no complications or recurrences have been observed in 7 years of follow-up. The main pathogenic theories and nomenclature are analyzed.

Surgical findings in idiopathic trigeminal neuropathy mimicking a trigeminal neurinoma.

Idiopathic trigeminal neuropathy is a benign disorder where the main clinical feature is facial numbness limited to the territory of one or more divisions of the trigeminal nerve, persisting for a few weeks to several years and in which no underlying disease can be identified. The case of a 37-year-old man with a brief history of sensory and motor trigeminal symptoms who showed magnetic resonance imaging (MRI) findings consistent with a small trigeminal neurinoma is reported. The patient was operated on but no tumour could be found during surgery and a biopsy was taken from the portio major. Pathological diagnosis was chronic non granulomatous inflammatory reaction with areas of coagulation necrosis. Control MRI showed complete resolution of the trigeminal abnormalities. It is concluded that in patients with MRI findings suggestive of a small trigeminal schwannoma, benign idiopathic trigeminal neuropathy should also be considered in the differential diagnosis. A conservative approach with sequential MRI studies may avoid an unnecessary surgical exploration.

[Lhermitte-Duclos disease in a ten-year-old child: clinical follow-up and neuroimaging data from birth]. / Enfermedad de Lhermitte-Duclos en un niño de 10 años: evolución clínica y de la neuroimagen desde el período neonatal.

INTRODUCTION: Lhermitte-Duclos disease is a rare lesion characterized by enlarged cerebellar folia containing abnormal ganglion cells. It typically affects young adults, and reports in the pediatric age are exceptional. CLINICAL CASE: This case report describes a child with slowly progressive macrocephaly, which was already present at birth, delayed motor development, and clumsiness. At 7 years of age a mild ataxia appeared, which remained stationary until 10 years of age when he developed signs of intracranial pressure (headache and papilloedema). A CT scan at 2 years of age showed an enlarged posterior fossa with asymmetrical cerebellum; another study at 7 years of age disclosed mild ventricular dilatation. IRM at 10 years of age showed aqueductal obliteration by an enlarged cerebellum. The cerebellar lesion consisted of abnormally thickened folia with abnormal hyperintensity of the central cerebellum on the T2-weighted images. The lesion did not enhance with gadolinium. The histological findings were typical of Lhermitte-Duclos disease. CONCLUSIONS: In our patient the lesion behaved like a slowly growing mass, but both neuroimaging and pathological studies were suggestive of a hamartomatous rather than a true neoplastic disorder. Furthermore, there was clinical evidence that the disorder was already present at birth. All the evidences in our case support the concept that this growing lesion represents a congenital abnormality.

Histochemical study of the vastus lateralis muscle fibre types of athletes.

In 16 women and 66 men, aged 14 to 36 years, 10 sedentary and 72 athletes, the histochemical characteristics of the vastus muscle fibres have been studied. Muscle biopsies were processed histochemically using the myofibrillar ATPase method, and were classified according to gender, sport activity and type of exercise. The average diameter of muscle fibres was larger in men than in women and in trained individuals than in sedentary ones. The largest percentage of Type I fibres was found in long distance runners; the smallest in those performing karate and triple jump. The largest percentage of Type IIA fibres was found in swimmers and the smallest in footballers. The largest percentages of Type IIB and IIC fibres were found in footballers. The largest average diameters of Type I and Type II fibres were found in swimmers and in long distance athletes respectively. Type I and Type II fibres were dominant in the aerobic group and the anaerobic one, respectively; the percentage of Type IIC fibres was smaller in the anaerobic group.

Primary progressive aphasia with glial cytoplasmic inclusions.

We report a 80-year-old woman who suffered from primary progressive aphasia for 3 years. Cranial CT and MRI studies showed moderate cerebral atrophy, more marked in the left frontal and temporal lobes, and SPECT brain scans revealed marked hypometabolism in the left frontal and temporal lobes. Neuropathologic examination of a temporal lobe biopsy demonstrated Gallyas-positive intracytoplasmic inclusions looking like fibrillary tangles and of Gallyas-positive cell processes, probably from glial cells. Glial intracytoplasmic inclusions were immunolabelled with antibodies to ubiquitin and with phosphorylion-dependent antitau antibodies, indicating the presence of hyperphosphorylated tau in the inclusions. There was only mild pathology of cortical neurons consisting in rare perikarya diffusely stained with antitau antibodies. There were no senile plaques, neurofibrillary tangles, 'achromatic' neurons, ballooned cells, Pick or Lewy bodies, nor microvacuoles or spongiform changes of the neuropil. The glial intracytoplasmic inclusions found in this case were similar to those found in multiple system atrophy, and differ from the cortical changes hitherto reported in primary progressive aphasia.

Rapidly deteriorating polyneuropathy associated with osteosclerotic myeloma responsive to intravenous immunoglobulin and radiotherapy.

Osteosclerotic myeloma is a plasma-cell dyscrasia characterized by osteosclerotic bone lesions, which may be associated with progressive demyelinating polyneuropathy. We describe a 49-year-old patient with rapidly deteriorating polyneuropathy associated with osteosclerotic myeloma, who responded favorably to a combination of intravenous immunoglobulin and radiotherapy.

1-Octadecene as a solvent for ferrofluids for intraocular use.

PURPOSE: 1-Octadecene is a hydrocarbon with one double bond in its structure that could serve as a solvent for ferrofluids. The aim of this pilot study was to obtain preliminary information on intraocular tolerance to 1-octadecene. METHODS: Vitreous compression with perfluoropropane gas was achieved in 20 eyes of albino rabbits. Four days after gas injection a fluid-gas exchange was undertaken. Sixteen eyes received 1-octadecene. Four eyes received balanced salt solution. Eyes were obtained at 3, 7, 14 and 30 days. The samples were fixed in 10% buffered formalin, processed in paraffin and sections were stained with hematoxylin and eosin. RESULTS: Emulsification of the oil bubble was observed in 31.25% of the cases by the fifth day; light microscopy showed normal retinal architecture in all the eyes and epiretinal and vitreous macrophages in 50% of the eyes. CONCLUSIONS: 1-Octadecene does not appear to have any retinal cytotoxic effect but elicits an inflammatory response in the vitreous activity.

Suprasellar papillary squamous craniopharyngioma. A case report.

Papillary squamous craniopharyngioma is an unusual variant of craniopharyngioma that presents almost exclusively in adults. We report a case of a 51-year-old man, who presented with visual and mental symptoms. A CT scan showed a suprasellar and intraventricular, uncalcified mass. After craniotomy a partly solid and cystic mass was resected. Light microscopy examination of the solid part shows a well-differentiated papillary squamous epithelium arranged in anastomosing cords and papillae. Peripheral palisading of cells, "stellate reticulum" and keratoid nodules were not present. No cholesterol clefts or calcifications are seen. The differential diagnosis of this tumor is discussed.