Dynamic and Cell-Specific DACH1 Expression in Human Neocortical and Striatal Development.

DACH1 is the human homolog of the Drosophila dachshund gene, which is involved in the development of the eye, nervous system, and limbs in the fly. Here, we systematically investigate DACH1 expression patterns during human neurodevelopment, from 5 to 21 postconceptional weeks. By immunodetection analysis, we found that DACH1 is highly expressed in the proliferating neuroprogenitors of the developing cortical ventricular and subventricular regions, while it is absent in the more differentiated cortical plate. Single-cell global transcriptional analysis revealed that DACH1 is specifically enriched in neuroepithelial and ventricular radial glia cells of the developing human neocortex. Moreover, we describe a previously unreported DACH1 expression in the human striatum, in particular in the striatal medium spiny neurons. This finding qualifies DACH1 as a new striatal projection neuron marker, together with PPP1R1B, BCL11B, and EBF1. We finally compared DACH1 expression profile in human and mouse forebrain, where we observed spatio-temporal similarities in its expression pattern thus providing a precise developmental description of DACH1 in the 2 mammalian species.

High rates of intestinal bicarbonate secretion in seawater tilapia (Oreochromis mossambicus).

Osmoregulation in fish is a complex process that requires the orchestrated cooperation of many tissues. In fish facing hyperosmotic environments, the intestinal absorption of some monovalent ions and the secretion of bicarbonate are key processes to favor water absorption. In the present study, we showed that bicarbonate levels in the intestinal fluid are several fold higher in seawater than in freshwater acclimated tilapia (Oreochromis mossambicus). In addition, we analyzed gene expression of the main molecular mechanisms involved in HCO3- movements i.e. slc26a6, slc26a3, slc4a4 and v-type H-ATPase sub C in the intestine of tilapia acclimated to both seawater and freshwater. Our results show an anterior/posterior functional regionalization of the intestine in tilapia in terms of expression patterns, which is affected by environmental salinity mostly in the anterior and mid intestine. Analysis of bicarbonate secretion using pH-Stat in tissues mounted in Ussing chambers reveals high rates of bicarbonate secretion in tilapia acclimated to seawater from anterior intestine to rectum ranging between ~900 and ~1700nmolHCO3-cm-2h-1. However, a relationship between the expression of slc26a6, slc26a3, slc4a4 and the rate of bicarbonate secretion seems to be compromised in the rectum. In this region, the low expression of the bicarbonate transporters could not explain the high bicarbonate secretion rates here described. However, we postulate that the elevated v-type H-ATPase mRNA expression in the rectum could be involved in this process.

A closer look at discordant placental echogenicity: two cases under the microscope.

Discordant placental echogenicity is observed in MC pregnancies complicated with twin anemia-polycythemia sequence, but could also belong to complicated singleton gestation.

Fetal pancreatic Langerhans islets size in pregnancies with metabolic disorders.

Objective: Metabolic disorders are a pandemic and increasing health problem. Women of childbearing age may also be affected, thus an abnormal metabolism may interfere with pregnancy short- and long-term outcomes, harming both mother and child. In the context of an abnormal maternal and intrauterine metabolic milieu the development of fetal organs, including pancreas, may be affected. Aim: To investigate the effects of pregnancy metabolic disorders on the morphology of pancreatic Langerhans islets in human late-third trimester stillborn fetuses. Methods: Samples from fetal pancreas underwent a quantitative histological evaluation to detect differences between pregnancy with (cases, n = 9) or without (controls, n = 6) abnormal metabolism. Results: Results show that the islets size increases in fetuses from dysmetabolic pregnancies and that this increment is related to both beta-cell hyperplasia and hypertrophy. Moreover, according to pregnancy and fetal metabolic disorders, a threshold of abnormal size of the islets has been identified. Above this threshold the size of fetal pancreatic Langerhans islets should be considered excessively increased. Conclusion: The study suggests that an accurate fetal pancreas analysis supplies an important tool in stillborn fetus, to discover metabolic disturbances that should be kept in mind and managed in future pregnancies.

M1 and M2 macrophages' clinicopathological significance in cutaneous melanoma.

Skin malignant melanoma (MM) is an aggressive cancer with an increasing incidence with limited therapies in advanced stages. Tumor-associated macrophages (TAMs) are the major immune constituent of the MM microenvironment and contribute toward its prognosis. TAMs' characterization and localization in human cancer is important to understand cancer progression and to identify molecular personalized therapies. M2 TAMs in stage I-II MMs are associated with worse prognostic parameters. A comprehensive M1-macrophage and M2-macrophage intratumoral localization and quantification in all stages of skin MMs is documented here with its clinical significance. To highlight immune pathways and possible early indicators of MM progression, we evaluated the number of M1 and M2 TAMs and intratumoral distribution in a large series of skin MMs. CD68 double immunostaining with MRP8-14 or inducible nitric oxide synthase (M1 macrophages) and with CD163 or CD204 (M2 macrophages) was performed in 94 stage I-IV skin MMs with a long duration of follow-up. The accumulation and distribution of M1 and M2 TAMs in intratumoral nests, stroma, and at the invasive front was correlated with clinicopathological variables. Since the early stage of MMs, M1 intratumoral macrophages were fewer than the M2 population; their recruitment was rapidly and progressively overwhelmed by an increase in M2 TAMs during MM progression. Independent of their intratumoral distribution, the accumulation of both M1 and M2 TAMs is associated with poor prognostic indicators and patients' survival. M1-recruited macrophages shift to the M2 phenotype early in MM development, possibly induced by high inducible nitric oxide synthase intratumoral increase peculiarly occurring since the initial MM stages. M2-recruited TAMs overwhelm M1 accumulation in all stages of MM progression, thus favoring neoplastic growth and dissemination. Independent of their intratumoral distribution, the prevalent accumulation of M2 TAMs in MM is statistically confirmed to be a poor indicator of patients' outcome and a potential target of immune therapies.

Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome.

Cornelia de Lange Syndrome (CdLS) is a choesinopathy: a severe genetic disorder caused by mutations in the cohesin complex genes. The phenotype is characterized by typical facial dysmorphism, growth impairment and multiorgan abnormalities including brain alterations. Wnt pathway is known to play a fundamental role in central nervous system development and it has been shown that Wnt pathway is disrupted in CdLS animal models and patients cells. In this review we investigate the possible link between Wnt pathway disruption and brain abnormalities in Cornelia de Lange Syndrome as such molecular impairment could lead to an abnormal embryonic development resulting in brain abnormalities (i.e. microcephaly, cerebellar hypoplasia, abnormal cortical development) in patients with Cornelia de Lange Syndrome.

Dimensional psychopathology of depression: detection of an 'activation' dimension in unipolar depressed outpatients.

BACKGROUND: Despite the high prevalence of bipolar spectrum disorders, most instruments currently available for the assessment of depression do not explore symptoms of 'activation' such as anger, irritability, aggressiveness, hostility, and psychomotor activation. METHODS: Two samples of adults with unipolar depression were studied. They had no comorbid DSM-IV disorder, and they were free from antidepressant drugs. The first sample (n = 380) was assessed with the SVARAD, a validated scale for the rapid assessment of the main psychopathological dimensions. The second sample (n = 143) was assessed with the MMPI-2. Factor analysis was performed on SVARAD items and MMPI-2 clinical scales. RESULTS: In both samples, we obtained a three-factor solution with factors interpreted as a depressive dimension, an anxious dimension, and an activation dimension. The latter dimension appeared to be clinically relevant in 20-27% of patients. LIMITATIONS: The presence of a comorbid disorder may have been missed in some cases. Also, some bipolar II patients might have been misdiagnosed as unipolar and included in the study. Further, our findings apply only to a selected psychiatric population, and it should be tested whether they generalize to other settings of care and other countries. CONCLUSIONS: Our results suggest that depressive mixed states are not rare even in patients diagnosed as unipolar, and that some unipolar patients might actually be 'pseudounipolar' and belong to the bipolar spectrum. More in general, our findings suggest that some depressed patients have prominent symptoms of activation that can easily go unnoticed using instruments that do not explore such symptoms. Detecting these symptoms has important treatment implications.

Changes with age in cerebral capillary morphology.

Age related alterations in cerebral capillary morphology were investigated in 4-, 10-, and 20-year-old Macaque monkeys and in 1-, 14-, 35-, 180-, and 800-day-old Sprague-Dawley rats. This study revealed the following changes with increasing age: a significant decrease in cerebral capillary wall thickness in frontal cortex in monkeys but not in rats; a significant increase in the thickness of basal lamina (BL) of cerebral capillaries in rats but not in monkeys, however there was a marked increase in this parameter in the monkey between 4 and 10 years of age; a significant decline in cerebral capillary endothelial mitochondrial content in monkeys whereas a significant decline in this parameter in rats was found only when the peak content at 35 days was contrasted with that at 800 days of age; and, aberrant tight junctions and thickened BL in one of five 20-year-old monkeys. These findings suggest impairment of barrier characteristics of cerebral capillaries with increasing age in both the rat and the monkey.

Effect of ethanol on synaptosomal sialic acid metabolism in the developing rat brain.

The total, glycoprotein-bound and glycolipid-bound sialic acid concentration, ad the activities of ecto-sialyltransferase and neuraminidase were determined in synaptosomes from preweanling ethanol-treated and control rats. The period of treatment corresponded to that of maximal synaptogenesis and peak synthesis of sialoglycocompounds (days 27-37 postconception). The average of the peak blood ethanol concentration was 271 mg/100 ml. In the ethanol-treated animals the sialic acid concentration was significantly reduced (approximately 20%) with an equally distributed decrease of glycoprotein- and glycolipid-bound sialic acid. The activity of ecto-sialyltransferase with asialofetuin as exogeneous acceptor was significantly diminished (about 30%) in the ethanol-treated pups. Neuraminidase showed an unchanged activity after correction for the reduction of endogeneous sialic acid substrate concentration. The total protein and lipid concentrations of the synaptosomal preparations did not differ between the groups. These results suggest that ethanol treatment during on of the vulnerable periods of brain development causes an inhibition of the incorporation of sialic acid into synaptosomal membrane-bound sialoglycocompounds. Such an effect of ethanol exposure might disturb intercellular interactions and the functional performance of the membrane during development, and could be of importance in the pathogenesis of the central nervous system manifestations of the fetal alcohol syndrome.

Psychopathological dimensions of depression: a factor study of the 17-item Hamilton depression rating scale in unipolar depressed outpatients.

BACKGROUND: Agreement on the factor structure of the Hamilton Depression Rating Scale (HDRS) has not been consistent among studies, and some investigators argued that the scale's factor structure is not reliable. This study aimed at shedding more light on this debated issue. METHODS: We studied 186 adults with unipolar depression (Major Depressive Disorder, n=80; Dysthymic Disorder, n=71; Depressive Disorder Not Otherwise Specified, n=25; Adjustment Disorder, n=10). They had no comorbid DSM-IV axis I or axis II disorders, and had received no treatment with antidepressant drugs in the previous 2 months. The factor structure of the scale was studied using the principal factor method, followed by oblique rotation. Factor scores were computed for each subject using the regression method. RESULTS: Using the scree-test criterion for factor extraction, we obtained a four-factor solution, explaining 43.8% of total variance. The four factors extracted were identified as (1) somatic anxiety/somatization factor; (2) a psychic anxiety dimension; (3) a pure depressive dimension; and (4) anorexia factor. Patients with Major Depressive Disorder scored significantly higher than patients with other diagnoses on the pure depressive dimension. LIMITATIONS: These results need to be replicated in different cultures, using analogous factoring techniques. CONCLUSIONS: Though not exhibiting factorial invariance in the stricter sense of the term, the 17-item HDRS did exhibit a relatively reliable factor structure. Our analysis provides further evidence that the scale is multidimensional. However, as long as the multidimensional character of the scale is taken into account the scale should be able to play a useful role in clinical research.

Blood-brain barrier, aging, brain blood flow, and sleep.

We have shown that significant ultrastructural changes occur with increasing age in the BBB in the nonhuman primate. It is probable that similar changes occur in aging humans. Clearly, morphophysiological changes, i.e., structural changes in cerebral capillaries, may alter the BBB mechanism as well as capillary perfusion which, in turn, may affect cerebral energy metabolism and neuronal function. Thus neurological function may be affected and sensitive indices of function such as sleep patterns altered.

Anaplastic thyroid carcinoma in a 49 year-old woman with a long-standing goiter. A case report.

A 49 year-old woman with anaplastic thyroid carcinoma came, for the first time, to our clinic with an enlarged supraclavicular lymph node. Ten years earlier she received a diagnosis of benign nodular goiter and has been followed up with ultrasonography, which never demonstrated any enlargement of her thyroid nodule and with fine needle aspiration biopsies (FNAB), that always proved normal. An ultrasonographic control, performed 10 months before diagnosis, showed the onset of a shell calcification all around the thyroid nodule that forbade the performance of FNAB. At initial examination in our endocrinology centre she was found to have an enlarged thyroid nodule (changing from 3.5 cm to 4.5 cm) and a supraclavicular lymph node 3 cm wide. The patient was therefore sent to the surgeon who performed a total thyroidectomy and a lymph node exenteration. The histological examination reported a thyroid anaplastic carcinoma, composed of osteoclast-like cells and large calcifications, which showed signs of local invasion and vessel infiltration; the supraclavicular lymph node proved to be a large metastasis of anaplastic thyroid cancer. Total body CT scan, bone scintigraphy and brain CT scan showed, respectively, lung, bone and brain metastasis. Postoperative chemotherapy was rapidly interrupted for acute toxicity. The patient died for lung, bone and brain metastasis, 2 months after initial examination.

[Ulcerative rectocolitis diagnosed in the elderly. Case studies]. / La rettocolite ulcerosa diagnosticata nell'anziano. Contributo casistico.

Fourteen patients with idiopathic ulcerative colitis (UC) diagnosis made over 60 years of age have been extrapolated from 255 (5.49%) consecutive. Some clinical parameters (sex; symptoms of onset; delay in diagnosis; extension of disease; density of relapses; therapy with cortisone) have been compared between the 14 patients with ultra sixtieth year of age diagnosis (A group) and the 241 patients with a diagnosis made previously (B group). There were no significant differences concerning the symptoms at onset and the delay in diagnosis. In group A a larger prevalence of the male (M/F 3.66 against 1.46) and distal localization (64% against 53%) have been reported. The density of relapse and therapy with cortisone (p < 0.025) prevailed in B group. In conclusion, limited to our experience, the UC in A group is less severe than in B group.

Attachment and detachment processes as a typological index of relational systems.

Attachment and detachment processes, as defined by modern attachment theories, place them as integrative between innate and acquired behaviors, like a regulatory system for every close relationship. As a consequence, family attachment styles, which proceed-throughout development-together with personal identity construction processes, stress the notion of relationship as a dialectical and interactive process, defining the irreducible duality of human experience, in which the personal individuality construction is linked, since the earliest phases of life, to the significant relationships. Dysfunctional patterns of attachment and detachment and self-construction processes interact in defining personal organizations one can observe in psychopathological situations; some clinical examples are proposed.

[Asymptomatic lithiasis of the common bile duct: diagnostic difficulty and essentiality of intraoperative cholangiography]. / La litiasi asintomatica della via biliare principale: difficoltà diagnostiche ed irrinunciabilità della colangiografia intraoperatoria.

Biliary lithiasis is a widespread pathology the diagnosis of which, following the introduction of ultrasonography, is increasingly easy. The frequent possibility of association between gallstones and choledocholithiasis, demands pre- or intraoperative recognition. The inadequacy of ultrasonography in excluding lithiasis of the common biliary tract with certainty, notwithstanding its other unquestionable advantages, and the disproportionate costs and risks of other investigations (cholangiography, ERCP, ecc.) which are such as to discourage routine use, confirm the role of operative cholangiography in the diagnosis of asymptomatic choledocholithiasis, so permetting its treatment. Personal experience of 100 consecutive cases of gallstones which showed fully 10 of them to be negative to preoperative investigation were found to have lithiasis of the common biliary tract.

[Acute cholecystitis: surgical treatment]. / La colecistite acuta: trattamento chirurgico.

Personal experience in the observation of 177 patients suffering from acute cholecystitis and treated in the five-year period 1981-1985 is reported. In particular, problems related to surgical treatment are pointed out.

Molecular and functional definition of the developing human striatum.

The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal genes, including those encoding transcription factors, that distinguished striatal from neocortical identities. Unexpected differences from mouse striatal development were discovered. We monitored 36 determinants at the protein level, revealing regional domains of expression and their refinement, during striatal development. We electrophysiologically profiled human striatal neurons differentiated in vitro and determined their refined molecular and functional properties. These results provide a resource and opportunity to gain global understanding of how transcriptional and functional processes converge to specify human striatal and neocortical neurons during development.

An imbalance of COX level is not related to placental abruption.

AIMS: Muscularised basal plate arteries (MA) or chorioamnionitis (CA) are often present in placental abruption. The aim of this study was to evaluate the placental expression of COX 1 and COX 2 in cases of placental abruption with MA or CA hypothesising that an imbalance in COX placental expression might be implicated in its pathogenesis. METHODS: COX 1 and COX 2 placental immunostaining was analysed in 16 placentas with abruption (nine with MA, seven with CA), in 26 normal placentas and in 10 gestational age-matched MA or CA cases without abruption. RESULTS: COX 1 and COX 2 protein expression was observed in all cases, both in placental abruption and in normal placentas. No differences in distribution of immunoreactivity were observed either between cases and controls or between MA and CA. The mean COX 1 ratio between COX-positive cells and all stromal cells was significantly lower in placental abruption with MA (0.14±0.05) when compared with cases with CA (0.35±0.06) and normal placenta (0.23±0.02; p<0.001). The mean COX 2 ratio was lower in placental abruption with MA than in normal placenta (0.09±0.06 vs 0.18±0.05: p<0.001). In contrast, no difference in COX 1 and COX 2 ratio was observed between MA cases with or without abruption and between CA cases with or without abruption. CONCLUSIONS: It is hypothesised that an imbalance of normal COX level may be present in cases with MA and CA but it is not related to placental abruption.