First clinical evaluation of the safety and efficacy of tarumase for the debridement of venous leg ulcers.

We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing.

Promoter hypermethylation of RARB and GSTP1 genes in plasma cell-free DNA as breast cancer biomarkers in Peruvian women.

Background: Promoter hypermethylation is one of the enabling mechanisms of hallmarks of cancer. Tumor suppressor genes like RARB and GSTP1 have been reported as hypermethylated in breast cancer tumors compared with normal tissues in several populations. This case-control study aimed to determine the association between the promoter methylation ratio (PMR) of RARB and GSTP1 genes (separately and as a group) with breast cancer and its clinical-pathological variables in Peruvian patients, using a liquid biopsy approach.

Whole exome sequencing in a sample of Peruvian patients diagnosed with epidermolysis bullosa.

Background: Epidermolysis bullosa (EB) is a complex and heterogeneous dermatological disease. Four main types of EB have been described, each of them with distinct characteristics: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler EB (KEB). Each main type varies in its manifestations, severity, and genetic abnormality.

Chip-based digital Polymerase Chain Reaction as quantitative technique for the detection of mutations in breast cancer patients.

Background: is a gene frequently mutated in breast cancer. With the FDA approval of alpelisib, the evaluation of for activating mutations is becoming routinely. Novel platforms for gene analysis as digital PCR (dPCR) are emerging as a potential replacement for the traditional Sanger sequencing.

Tracing the genetic history of the 'Cañaris' from Ecuador and Peru using uniparental DNA markers.

Background: According to history, in the pre-Hispanic period, during the conquest and Inka expansion in Ecuador, many Andean families of the Cañar region would have been displaced to several places of Tawantinsuyu, including Kañaris, a Quechua-speaking community located at the highlands of the Province of Ferreñafe, Lambayeque (Peru). Other families were probably taken from the Central Andes to a place close to Kañaris, named Inkawasi. Evidence of this migration comes from the presence near the Kañaris-Inkawasi communities of a village, a former Inka camp, which persists until the present day.

Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

Introduction: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care.

Genetic ancestry of families of putative Inka descent.

This study focuses on the descendants of the royal Inka family. The Inkas ruled Tawantinsuyu, the largest pre-Columbian empire in South America, which extended from southern Colombia to central Chile. The origin of the royal Inkas is currently unknown.

Mutational analysis of and genes in Peruvian families with hereditary breast and ovarian cancer.

Background: Breast cancer is one of the most prevalent malignancies in the world. In Peru, breast cancer is the second cause of death among women. Five to ten percent of patients present a high genetic predisposition due to and germline mutations.

The volumes of the fornix in schizophrenia and affective disorders: a post-mortem study.

Structural and functional pathology of limbic structures including the hippocampus are frequently replicated in schizophrenia. Although the fornix is the main afferent system of the hippocampus to the septal nuclei and the hypothalamus (especially the mammillary bodies), relatively few studies have investigated structural changes of the fornix in schizophrenia. We measured the volume of the fornix in post-mortem brains in 19 patients with schizophrenia, 9 patients with bipolar disorder, 7 patients with unipolar depression, and 14 control subjects by planimetry of serial sections.

Differential parametric modulation of self-relatedness and emotions in different brain regions.

Our sense of self is strongly colored by emotions although at the same time we are well able to distinguish affect and self. Using functional magnetic resonance imaging, we here tested for the differential effects of self-relatedness and emotion dimensions (valence, intensity) on parametric modulation of neural activity during perception of emotional stimuli. We observed opposite parametric modulation of self-relatedness and emotion dimensions in the dorsomedial prefrontal cortex and the ventral striatum/nucleus accumbens, whereas neural activity in subcortical regions (tectum, right amygdala, hypothalamus) was modulated by self-relatedness and emotion dimensions in the same direction.

[Recurrent dysregulation of body temperature during antipsychotic pharmacotherapy].

Objective: This case report presents a rare, potentially life-threatening vegetative disturbance, which can occur during pharmacotherapy of schizophrenia.

Method: A retrospective descriptive transversal and longitudinal section consideration of in-patient treatments of one female was performed.

Results: A 50-years old woman suffering from oligophrenia and disorganized psychosis (ICD-10: F71, F20.

Influence of vigilance and learning on prefrontal activation in schizophrenia.

Background: Executive functions, which are neuroanatomically associated with the frontal lobe, are known to be impaired in schizophrenia. It is, however, still unclear whether the underlying functional disturbance is due to a hyper- or a hypoactivation of the dorsolateral prefrontal cortex (DLPFC) or neither.

Methods: To address this question, we examined the brain activation of 21 schizophrenic patients on atypical antipsychotic medication and 21 healthy control subjects during a mental maze task by means of fMRI.

Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia: further evidence for limbic neuropathology.

The mammillary bodies (MB) are important relay nuclei within limbic and extralimbic connections. They are known to play important roles in memory formation and are affected in alcoholism and vitamin B1 deficiency. Their strategic position linking temporo-limbic to cortico-thalamic brain structures make the MB a candidate brain structure for alterations in schizophrenia.

Brain activation during mental maze solving.

Background: So-called Porteus mazes are used to investigate prefrontal cortex (PFC) functioning in normal subjects and patients with different neuropsychiatric disorders. Here we present data confirming the involvement of the PFC for the first time by means of functional magnetic resonance imaging (fMRI). To minimize motor-related activation, mental mazes were used.

Volume and neuron number of the mediodorsal thalamic nucleus in schizophrenia: a replication study.

Previous neuropathological studies on the mediodorsal thalamic nucleus (MD) in schizophrenia have yielded conflicting results. While some studies suggested that patients with schizophrenia have a pronounced reduction of the volume and neuron number in the MD, more recent data have not found anatomical alterations in this thalamic nucleus. However, most studies have considerable methodological shortcomings.

Volume deficits of subcortical nuclei in mood disorders A postmortem study.

Structural changes in subcortical nuclei may underlie clinical symptoms of mood disorders. The goal was to determine whether macrostructural changes exist in brain areas assumed to be involved in regulation of mood and whether such changes differ between major depressive disorder and bipolar disorder. A case-control design was used to compare volumes of all major subcortical nuclei.

[Pathology of the thalamus and schizophrenia--an overview].

Since the beginning of the 20 (th) century, the thalamus was regarded as a brain region which may be involved in the pathogenesis of schizophrenia. Distinct thalamic nuclei were morphologically analyzed with qualitative methods with an emphasis on the mediodorsal nucleus. However, the reported results were inconsistent.

Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation.

Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI).

Fewer beta-endorphin expressing arcuate nucleus neurons and reduced beta-endorphinergic innervation of paraventricular neurons in schizophrenics and patients with depression.

In order to elucidate whether the hypothalamic expression of beta-endorphin is altered in patients with mental disorders we studied the cellular localization of the peptide in arcuate nucleus neurons as well as the beta-endorphinergic innervation of paraventricular neurons in nine schizophrenics, six subjects with depression, and nine controls. A polyclonal antiserum against beta-endorphin was employed for the immunohistochemical detection of the peptide in sections of postmortem human brains. Quantitative analysis revealed that the number of beta-endorphin-containing arcuate neurons was statistically reduced in schizophrenics and depressives in comparison to controls.

Volumes of association thalamic nuclei in schizophrenia: a postmortem study.

The major association thalamic nuclei, the mediodorsal nucleus (MD) and the medial pulvinar nucleus (PUM) are regarded as important parts of the circuits among association cortical regions. Association cortical regions of the frontal, parietal and temporal lobes have been repeatedly implicated in the neuropathology of schizophrenia. Thus, the aim of the present postmortem study was to investigate the volumes of association thalamic nuclei in this disease.

Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients.

The cellular expression of nitric oxide synthase (NOS) was studied in neurons of the Nuc. suprachiasmaticus (SCN) of depressed patients and matched controls. The number of NOS-immunoreactive SCN neurons was significantly reduced in depression.

Increased number of nitric oxide synthase immunoreactive Purkinje cells and dentate nucleus neurons in schizophrenia.

There is growing interest in the cerebellum as a site of neuropathological changes in schizophrenia. Reports showing that schizophrenics have higher nitric oxide synthase (NOS) activity and MAPKinase levels in the vermis, point to possible aberrations in the cerebellar signal transduction of schizophrenics. It has been speculated that Ca(2+)-dependent extracellular to intracellular signal transduction may be disrupted in the cerebellum of schizophrenics.

Serum concentration of chlormethiazole and therapeutic effect in acute alcohol withdrawal syndrome: an open clinical trial.

It was the aim of this study to find a relationship between the serum concentration of chlormethiazole and its therapeutic effect in acute alcohol withdrawal syndrome. As a secondary subject, the concentration of chlormethiazole was investigated in relation to variables of treatment and variables of physical status of patients. In an open clinical trial, the clinical status of patients was rated by the Mainz Alcohol Withdrawal Scale (MAWS) and the Delirium Rating Scale (DRS).

Hippocampal expression of the calcium sensor protein visinin-like protein-1 in schizophrenia.

Hippocampal cytoarchitectural abnormalities may be part of the cerebral substrate of schizophrenia. Amongst the chemical components being abnormal in brains of schizophrenics are altered calcium concentrations and reduced expression of the neurotrophin receptor, trkB. We studied by immunohistochemical methods the distribution of visinin-like protein-1 (VILIP-1), which is a calcium sensor protein and at the same time a trkB mRNA binding protein, in hippocampi of nine schizophrenic patients and nine matched control subjects.