Differential Mueller matrix imaging of partially depolarizing optically anisotropic biological tissues.

Since recently, a number of innovative polarization-based optical imaging modalities have been introduced and extensively used in various biomedical applications, with an ultimate aim to attain the practical tool for the optical biopsy and functional characterization of biological tissues. The techniques utilize polarization properties of light and Mueller matrix mapping of microscopic images of histological sections of biological tissues or polycrystalline films of biological fluids. The main drawback of currently developed laser polarimetry approaches and Mueller matrix mapping techniques is poor reproducibility of experimental data. This is due to azimuthal dependence of polarization and ellipticity values of most matrix elements to sample orientation in respect to incidence light polarization. Current study aims to generalize the methods of laser polarimetry for diagnosis of partially depolarizing optically anisotropic biological tissues. A method of differential Mueller matrix mapping for reconstruction of linear and circular birefringence and dichroism parameter distributions of partially depolarizing layers of biological tissues of different morphological structure is introduced and practically implemented. The coordinate distributions of the value of the first-order differential matrix elements of histological sections of brain tissue with spatially structured, optically anisotropic fibrillar network, as well as of parenchymatous tissue of the rectum wall with an "islet" polycrystalline structure are determined. Within the statistical analysis of polarization reproduced distributions of the averaged parameters of phase and amplitude anisotropy, the significant sensitivity of the statistical moments of the third and fourth orders to changes in the polycrystalline structure of partially depolarizing layers of biological tissue is observed. The differentiation of female reproductive sphere connective tissue is realized with excellent accuracy. The differential Mueller matrix mapping method for reconstruction of distributions of linear and circular birefringence and dichroism parameters of partially depolarizing layers of biological tissues of different morphological structures is proposed and substantiated. Differential diagnostics of changes in the phase (good balanced accuracy) and amplitude (excellent balanced accuracy) of the anisotropy of the partially depolarizing layers of the vagina wall tissue with prolapse of the genitals is realized. The maximum diagnostic efficiency of the first-order differential matrix method was demonstrated in comparison with the traditional methods of polarization and Mueller matrix mapping of histological sections of light-scattering biological tissues.

Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice.

Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood-cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviors in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behavior. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder.

Spatial-frequency selection of complex degree of coherence of laser images of blood plasma in diagnostics and differentiation of pathological states of human organism of various nosology.

The theoretical background of correlation and phase analysis of laser images of human blood plasma with the spatial-frequency selection of the manifestations of mechanisms of linear and circular birefringence of albumin and globulin is presented. The comparative results of measuring the coordinate distributions of the module of complex degree of coherence (CDC) of laser images of blood plasma taken from the patients of three groups--healthy patients (donors), the patients suffering from the rheumatoid arthritis, and those with stomach cancer (adenocarcinoma)--are shown. The values and ranges of change of the statistical (moments of the first-fourth orders), correlation (excess of autocorrelation functions), and fractal (slopes of approximating curves and dispersion of the extremes of logarithmic dependencies of power spectra) parameters of CDC coordinate distributions are studied. The objective criteria of diagnostics of the pathology and differentiation of the inflammation and oncological state are determined.

Laser polarization autofluorescence of endogenous porphyrins of optically anisotropic biological tissues and fluids in diagnostics of necrotic and pathological changes of human organs.

This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections, cytological smears). The polarization structural properties of autofluorescent images of human biological tissues layers and fluids were found and investigated. A model describing the formation of polarizationally heterogeneous images of optically anisotropic biological layers is suggested. On this basis, the practical method of polarization-variable autofluorescence is analytically substantiated and experimentally tested. The efficiency of applying this method to various tasks of medical diagnostics is analyzed: objectification of histological conclusions, defining and differentiating of various forms of cancer (dysplasia--microinvasive cancer) of the cervix uteri, and forensic medical express-differentiation of cause of death. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections of myocardium biopsy and endometrium and cytological smears of its mucous tunic are defined. The operational characteristics (sensitivity, specificity, accuracy) of this method are determined concerning the positions of probative medicine, and the clinical efficiency of the technique is demonstrated.

Developmental alterations in CNS stress-related gene expression following postnatal immune activation.

Early-life adversity is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased susceptibility to later-life psychopathology. Specifically, there is mounting evidence suggesting that the immune system plays an important role in central nervous system (CNS) development and in the programing of behavior. The current study investigated how early-life immune challenge affects the development of CNS stress neurocircuitry by examining the gene expression profile of corticotropin-releasing hormone (CRH), CRH receptors, and the major corticosteroid receptors within the limbic-hypothalamic circuit of the developing rodent brain. Mice were administered a 0.05 mg/kg lipopolysaccharide (LPS) injection on postnatal day (P) 3 and 5 and gene expression was assessed using in situ hybridization from P14 to P28. Target genes investigated were CRH, CRH receptor-1 (CRHR1), CRH receptor-2, the mineralocorticoid receptor, and the glucocorticoid receptor (GR). Early LPS challenge resulted in a transient decrease in CRHR1 mRNA expression in the cornuammonis 1 (CA1) and CA3 regions of the hippocampus that were accompanied by increased hippocampal GR mRNA expression in the CA1 region between P14 and P21. This was followed by increased hypothalamic CRH expression in LPS-mice on P28. Our current findings suggest that early-life LPS challenge impacts the developmental trajectory of CNS stress neurocircuitry. These results lend insight into the molecular basis for the later development of stress-related behaviors as previously described in early immune challenge rodents.

A developmental characterization of mesolimbocortical serotonergic gene expression changes following early immune challenge.

An immunogenic challenge during early postnatal development leads to long-term changes in behavioural and physiological measures reflecting enhanced emotionality and anxiety. Altered CNS serotonin (5-HT) signalling during the third postnatal week is thought to modify the developing neurocircuitry governing anxiety-like behaviour. Changes in 5-HT signalling during this time window may underlie increased emotionality reported in early immune challenge rodents. Here we examine both the spatial and temporal profile of 5-HT related gene expression, including 5HT1A, 2A, 2C receptors, the 5-HT transporter (5HTT), and tryptophan hydroxylase 2 (TPH2) during early development (postnatal day [P]14, P17, P21, P28) in mice challenged with lipopolysaccharide (LPS) during the first postnatal week. Expression levels were measured using in situ hybridization in regions associated with mediating emotive behaviours: the dorsal raphe (DR), hippocampus, amygdala, and prefrontal cortex (PFC). Increased TPH2 and 5HTT expression in the ventrolateral region of the DR of LPS-mice accompanied decreased expression of ventral DR 5HT1A and dorsal DR 5HTT. In the forebrain, 5HT1A and 2A receptors were increased, whereas 5HT2C receptors were decreased in the hippocampus. Decreased mRNA expression of 5HT2C was detected in the amygdala and PFC of LPS-treated pups; 5HT1A was increased in the PFC. The majority of these changes were restricted to P14-21. These transient changes in 5-HT expression coincide with the critical time window in which 5-HT disturbance leads to permanent modification of anxiety-related behaviours. This suggests that alterations in CNS 5-HT during development may underlie the enhanced emotionality associated with an early immune challenge.

Infantile haemangiomas: a challenge in paediatric dermatology.

Infantile haemangiomas, common benign vascular tumours of childhood, are characterized by rapid growth during the first year of life and a slow regression that is usually completed at 7-10 years of age. These tumours are composed of endothelial cells with high mitotic rates and stromal components such as fibroblasts, mast cells and pericytes. Haemangiomas become a challenge when they are part of a syndrome, are located in certain areas of the body or when complications develop. The above-mentioned factors also influence the treatment modality used. However, although there remain many uncertainties regarding management, the beta-adrenergic receptor blocker propranolol is a promising new candidate for first-line systemic therapy. It produces such a dramatic and rapid response that the appearance of an infantile haemangioma should impart expeditious consideration of the risks and benefits of its use.

[Response of cerebral hemodynamics to combined stress impacts].

Changes in cerebral hemodynamics (CH) was assessed with transcranial color duplex scanning in the middle cerebral artery (MSA) of 15 healthy male volunteers aged 20-23 years in response to psychoemotional stress (PES). The latter was induced by calculations, mild exercise (Martine's test), hypercapnia in inspiration of 6% CO2 and their various combinations. The results showed that a combined action of the stressors differs quantitatively and qualitatively from their isolated action. As a rule, in combination the stressors potentiated each other. The response of CH to a combined action of the stressors, PES and hypercapnia, in particular, may be also characterized by a prevalent effect of one of the stressors, in this case by a stronger action of hypercapnia.

[Extracorporeal shock-wave therapy in the treatment of Peyronie's disease]. / Primenenie ékstrakorporal'noi udarno-volnovoi terapii v lechenii bolezni Peironi.

The authors analyse the results of treatment of 28 patients with Peyronie's disease using extracorporeal shock-wave lithotripsy (ESWL) performed on Dornier U15 lithotriptor. A total of 2-6 sessions were made, maximal number--12. The efficacy was controlled by clinical indices and ultrasonic investigation (Doppler mapping of the blood flow). ESWL proved to be efficient in the treatment of Peyronie's disease (PD), primarily, in patients with early disease before appearance of severe fibroplastic alterations. Less plaque vascularization by energetic Doppler mapping due to ESWL is an important diagnostic criterion of PD treatment efficacy. Conservative treatment is not indicated in marked deformities and plaque calcification, erectile dysfunction. Moreover, any injection into the tunica albuginea, especially complicated by hematomas may be a damaging factor which triggers fibrous inflammation. Such patients should be treated surgically. If the patient is interested in immediate results or is not interested in continuation of sexual life, the treatment is prognostically uneffective. Thus, ESWL is an effective, safe method of PD treatment but requires further study and accumulation of clinical experience.

Conformational analysis of a novel cyclic enkephalin analogue using NMR and EDMC calculations.

Conformational space of a novel cyclic enkephalin analogue, cyclo(N(epsilon),N(epsilon')-carbonyl-D-Lys2,Lys5)enkephalin amide, was exhaustively examined. A large number of conformations was selected and clustered into families on the basis of their structure and energy. For representative conformations ROESY spectra were generated and their linear combination was fitted to the spectra measured in water and Me2SO-d6. This procedure yielded an ensemble of most populated conformations of the peptide in the two solvents.

[Struma ovarii: an ovarian neoplasm]. / Struma ovarii--nowotwór jajnika.

Authors shows three cases of very rarely occurring ovarian struma. First case--was discovered in a patient with normal physiological hormonal activity. Second case--was discovered in a postmenopausal patient with hyperthyroidism and with endometrial carcinoma. Third case--was discovered in a postmenopausal patient, without any complaints, where an ovarian tumor was found during periodical gynaecological examination. Histopathological evaluation of the material was decisive for the final diagnosis.

Classification of proximal humerus fractures: The contribution of the scapular lateral and axillary radiographs.

Trauma series radiographs of 50 proximal humerus fractures were used to assess the relative contribution of the scapular lateral and axillary radiographs to fracture classification with the Neer system. The radiographs were reviewed by an orthopaedic shoulder specialist, on orthopaedic traumatologist, a skeletal radiologist, and orthopaedic residents in their fifth and second years, respectively, of postgraduate training. In the first viewing radiographs were reviewed and classified in the following sequence: (1) after scapular anteroposterior view alone; (2) after review of scapular anteroposterior and lateral views; and (3) after review of scapular anteroposterior, lateral, and axillary views. A second viewing of the same 50 cases was performed 6 months later in a changed sequence: (1) after scapular anteroposterior view alone; (2) after review of scapular anteroposterior and axillary views; and (3) after review of scapular anteroposterior, axillary, and scapular lateral views. For the five observers, review of the scapular anteroposterior and axillary views achieved the final classification in 99% of cases. However, after review of the scapular anteroposterior and lateral views, the final classification was achieved in only 79% of cases (p < 0.05). These results indicate that when combined with the scapular anteroposterior radiograph, the axillary view contributes significantly more to fracture classification with the Neer system than the scapular lateral radiograph.

The Neer classification system for proximal humeral fractures. An assessment of interobserver reliability and intraobserver reproducibility.

The radiographs of fifty fractures of the proximal part of the humerus were used to assess the interobserver reliability and intraobserver reproducibility of the Neer classification system. A trauma series consisting of scapular anteroposterior, scapular lateral, and axillary radiographs was available for each fracture. The radiographs were reviewed by an orthopaedic shoulder specialist, an orthopaedic traumatologist, a skeletal radiologist, and two orthopaedic residents, in their fifth and second years of postgraduate training. The radiographs were reviewed on two different occasions, six months apart. Interobserver reliability was assessed by comparison of the fracture classifications determined by the five observers. Intraobserver reproducibility was evaluated by comparison of the classifications determined by each observer on the first and second viewings. Kappa (kappa) reliability coefficients were used. All five observers agreed on the final classification for 32 and 30 per cent of the fractures on the first and second viewings, respectively. Paired comparisons between the five observers showed a mean reliability coefficient of 0.48 (range, 0.43 to 0.58) for the first viewing and 0.52 (range, 0.37 to 0.62) for the second viewing. The attending physicians obtained a slightly higher kappa value than the orthopaedic residents (0.52 compared with 0.48). Reproducibility ranged from 0.83 (the shoulder specialist) to 0.50 (the skeletal radiologist), with a mean of 0.66. Simplification of the Neer classification system, from sixteen categories to six more general categories based on fracture type, did not significantly improve either interobserver reliability or intraobserver reproducibility.

Humeral lengthening and bone transport using the Ilizarov technique.

The authors present their results of Ilizarov treatment of eight humeral length deficits and bone defects in seven consecutive patients treated at the Hospital for Joint Diseases. The mean humeral lengthening achieved was 9.8 cm. The lengthening goal was completely achieved in six cases, while two cases achieved over 80% of the desired length. No permanent neurovascular or infectious complication occurred. The authors suggest that the Ilizarov technique is a viable method in treating severe humeral length deficits or bone defects.

Spontaneous bronchopneumonia in laboratory dogs infected with untyped Mycoplasma spp.

Three Mycoplasma spp. were isolated from five colony bred laboratory dogs (Canis familiaris) obtained from a single vendor. Four of these animals were Beagles and one was a mongrel. Three displayed clinical signs of respiratory disease including dyspnea, chronic coughing and moist rales, while the other two dogs were observed during thoracic surgery to have macroscopic lesions suggestive of pneumonia. All five dogs were submitted for diagnostic necropsy during which they were cultured for bacteria and mycoplasma. Mycoplasma spp. having three distinct colonial forms were isolated from the lungs of each of the animals. These three isolates were sent to the National Cancer Institute Diagnostic Microbiology Laboratory and to the National Institutes of Health, NIAID, Mycoplasmology Laboratory. Neither laboratory could serotype these isolates against antisera to 73 Mycoplasma spp., including the common canine mycoplasmas, and nine Acholeplasma spp. Histologically, the bronchopneumonia was characterized by bronchiectasis, purulent bronchiolitis, bronchial and bronchiolar epithelial hyperplasia, chronic non-suppurative peribronchiolitis and perivasculitis, bronchiolitis obliterans, and acute to subacute purulent pneumonia. The similarity between the pathologic findings in these animals and those observed in respiratory mycoplasmosis of other species, e.g. the rat, suggests a causal relationship between the isolated mycoplasmas and the pulmonary disease observed in these dogs.

Pasteurella pneumotropica in rabbits from a "Pasteurella-free" production colony.

Pasteurella pneumotropica was isolated from the nasopharyngeal area of two of five rabbits obtained from a "Pasteurella-free" production colony. No evidence of disease was observed in these rabbits during clinical and necropsy examinations.