Thermo-rheological responsive microcapsules for time-dependent controlled release of human mesenchymal stromal cells.

Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermo-responsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.

[ABERRANT RIGHT SUBCLAVIAN ARTERY (ARSA)--A NEW ULTRASOUND MARKER FOR CHROMOSOMAL FETAL ABNORMALITIES].

UNLABELLED: The development of the fetal aorta ends with the formation of the aortic arch which normally branches into three blood vessels: 1) a. brachiocephalica (a. innominata), which divides into the right subclavian artery (RSA) and the right carotid artery; 2) the left carotid artery; and 3) the left subclavian artery. Occasionally, RSA originates as a separate fourth branch of the aortic arch, passing behind the trachea with an oblique course to the right shoulder. This rare variant is called an aberrant right subclavian artery (ARSA) and is observed in approximately 2% of normal individuals. On the other hand, the reported incidence of ARSA varies between 25 and 37% in cases with Down syndrome and other chromosomal abnormalities. OBJECTIVE: To evaluate the success rate of ultrasound visualization of the fetal RSA between 18 and 23 weeks of gestation and to establish the importance of the prenatal diagnosis of ARSA in the risk assessment for fetal chromosomal abnormalities in the second trimester. RESULTS: Three experienced sonographers scanned 992 fetuses in MC "Markovs", Sofia between 01.09.2013-01.06.2014 with Voluson 730 Expert (GE Healthcare) ultrasound equipment. Visualization of RSA was successful in 92.7% of cases. Overall, 17 cases with ARSA were diagnosed in the study period. ARSA was an isolated sonographic finding in 13 of them. The remaining 4 cases had additional pathology. In the first case ARSA was associated with a short femurand humerus, short nasal bone and borderline nuchal thickness without any other soft markers or structural abnormalities. Trisomy 21 was diagnosed after amniocentesis and the pregnancy was terminated at patient's request. In the second case ARSA was associated with severe polymalformation syndrome. Trisomy 18 was diagnosed by DNA analysis post abortem. In the third case ARSA was associated with an unilateral cleft lip and cleft palate. Abnormalities of the fetal karyotype and Di George syndrome were excluded by amniocentesis. The fourth case was associated with a single umbilical artery without any structural and chromosomal abnormalities. The pregnancy had a favourable perinatal outcome at term. CONCLUSION: Visualization of RSA and prenatal diagnosis of ARSA in the second trimester is relatively easy in experienced hands. The examination slightly prolongs the fetal morphology scan. Since there is an obvious association between ARSA and chromosomal fetal abnormalities, implementation of its sonographic evaluation in the protocol of fetal echocardiography in the second trimester is strongly recommended.

Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats.

The therapeutic efficacy of regular physical exercises in an animal model of epilepsy and depression comorbidity has been confirmed previously. In the present study, we examined the effects of endurance training on susceptibility to kainate (KA)-induced status epilepticus (SE), behavioral changes and neuronal damage in spontaneously hypertensive rats (SHRs). Male SHRs were randomly divided into two groups. One group was exercised on a treadmill with submaximal loading for four weeks and the other group was sedentary. Immediately after the training period, SE was evoked in half of the sedentary and trained rats by KA, while the other half of the two groups received saline. Basal systolic (SP), diastolic (DP) and mean arterial pressure (MAP) of all rats were measured at the beginning and at the end of the training period. Anxiety, memory and depression-like behaviour were evaluated a month after SE. The release of 5-HT in the hippocampus was measured using a liquid scintillation method and neuronal damage was analyzed by hematoxylin and eosin staining. SP and MAP of exercised SHRs decreased in comparison with the initial values. The increased resistance of SHRs to KA-induced SE was accompanied by an elongated latent seizure-free period, improved object recognition memory and antidepressant effect after the training program. While the anticonvulsant and positive behavioral effects of endurance training were accompanied by an increase of 5-HT release in the hippocampus, it did not exert neuroprotective activity. Our results indicate that prior exercise is an effective means to attenuate KA-induced seizures and comorbid behavioral changes in a model of hypertension and epilepsy suggesting a potential influence of hippocampal 5-HT on a comorbid depression. However, this beneficial impact does not prevent the development of epilepsy and concomitant brain damage.

[CLINICAL PERFORMANCE OF DIFFERENT METHODS FOR CERVICAL SCREENING].

UNLABELLED: Cervical cancer is a serious medical and social issue as it affects women at active age and it is diagnosed too late. In Bulgaria morbidity and mortality show continuous increasing trend. The aim of this study is to compare the clinical performance of cytology and other alternative methods for cervical screening that could be used to assess the the cervix. MATERIAL AND METHODS: This is a prospective study which included 317 patients aged between 18 and 65 years. Women were divided into four groups: I-st--cytology, Il-nd--visual inspection with acetic acid (VIA), III-th--visual inspection with Lugol's iodine (VILI) and IV-th--spectrophotometric analysis with TruScreen®. The results showed that the most appropriate screening method for cervical cancer remains cytology. In the absence of cytological laboratory or cytopathologist spectrophotometric analysis with TruScreen® can be used for primary cervical screening. Its main advantages are that it is a real time technique, user easy and it is well accepted by women. If TruScreen is not available in the gynecologist's practice it is possible to perform visual inspection with acetic acid (VIA).

Obesity in the news: directions for future research.

Obesity attracts large volumes of news coverage. This in turn has spawned academic studies investigating how news framing may affect views about causes of and solutions to obesity. We use key studies to demonstrate that although existing research has made valuable discoveries about how obesity is defined in various media outlets, some methodological and theoretical questions remain unaddressed. We argue that extant research has focused on one dimension of analysis--the problematization of obesity in news stories--precluding insights into the entire process of obesity communication. Drawing on framing and media studies research, we propose a multidimensional approach to shed more light on factors affecting the production of obesity news stories by journalists and how they may be received by audience members. Ways of moving research into this multidimensional direction are proposed, including analysis of journalistic news values, political leaning and style of media outlets, emotion-eliciting language, readers' comments and obesity-related news visuals. Knowledge resulting from the exploration of these dimensions of the issue of obesity can be used to improve strategies to inform and engage audience members.

[First trimester cystic structures in the fetalabdomen: diagnosis and prognostic value].

AIM: To define the major sonographic findings used in the diagnosis and differential diagnosis of fetal abdominal cysts in the first trimester and to establish their clinical relevance to the perinatal outcome. METHODS: A prospective longitudinal study of 5 antenatally detected cases of fetal abdominal cysts between 11-14 w.g. was performed in the University Hospital of Obstetrics and Gynecology "Maichin dom" and MC "Markovs", Sofia between Jan 2007 and Aug 2009. In all cases color flow mapping was used to differentiate the cystic structure from the fetal bladder by identifying the two umbilical arteries. All continuing pregnancies were carefully followed up sonographically at 14-16 w.g, 18-22 w.g. and 28-32 w.g., including with fetal echocardiography. Genetic amniocentesis was offered in all cases to exclude associated chromosomal abnormality. Termination of pregnancy was an option in all affected cases. Information about the perinatal outcome was ascertained by the hospital records, the referring physicians and/or the patients themselves. RESULTS: There were 5 cases of fetal abdominal cysts diagnosed between 11-14 w.g. during the study period (2--megacystis, 3--cystic structures from the gastro-intestinal tract). In one case of megacystis the patients opted for termination of pregnancy at 15 w.g. The second affected case was a male fetus from a twin pregnancy. The patient delivered at term by Cesarean section with a subsequent surgical treatment of the newborn. In one of the remaining three cases of fetal abdominal cysts the patients opted for termination of pregnancy at 12 w.g. The other two were followed up sonographically. Eventually, a complete resolution of the cystic structure was demonstrated. Both newborns had an uneventful perinatal outcome and were delivered at term with no complications in the early neonatal period. CONCLUSION: Megacystis is a common fetal abdominal cyst in early pregnancy. Abdominal cysts with other origin often resolve spontaneously or remain small in the second and third trimester. Thus, they usually have a good perinatal outcome. Nevertheless, some first trimester fetal abdominal cysts can be associated with structural abnormalities or other complications from the gastrointestinal tract.

[Three-dimensional sonoembryology--myth or reality].

OBJECTIVE: To describe the normal development of the embryonic central nervous system (CNS) using three-dimensional (3D) transvaginal (TV) ultrasound (US) between 7 and 10 w.g. and to compare the embryonic development visualized by 3D TV US with that of the classical embryology. METHODS: A prospective longitudinal study was conducted over a period of 10 months with high-end ultrasound equipment (Voluson 730 Expert, GE Healthcare, U.S.). Thirty six pregnant women between 7 and 10 weeks of gestation (w.g.) were examined. In all cases a high-frequency 30 TV probe was used to acquire a 3D volume of the embryo, including the cranial pole. Subsequently, the acquired volume information was post-processed and analyzed with specialized software 4D View ver. 9.1 (GE Healthcare, U.S.). The duration of the examinations was about 15 minutes. RESULTS: Three-dimensional TV US allows adequate visualization of the embryonic CNS in accordance with the Carnegie stages from the classical embryology. In 7 w.g. it is possible to identify the diencephalon (future third ventricle), mesencephalon (future aqueductus Sylvii), rhombencephalon (future fourth ventricle), and the two hemispheres. In 8 w.g. the choroid plexus in the lateral ventricles, the fourth ventricle and the cerebellum can also be recognized. The developmental changes in the size, shape and relationship of the described structures can be progressively assessed in 9 and 10 w.g. CONCLUSIONS: Implementation of high-frequency 3D TV probes allows good visualization of the developing embryo, detailed anatomical description of all main cerebral structures, as well as adequate reconstruction of the brain ventricular system between 7 and 10 w.g. There is a good correlation between the embryonic development visualized by 3D TV U.S. and that of the classical embryology.

[Absent intracranial translucency--new ultrasound marker for spina bifida at 11-13+6 weeks of gestation].

Spina bifida is the most common abnormality of the fetal central nervous system. Prenatal diagnosis is usually made by ultrasound in the second or third trimester of pregnancy. However, first trimester detection of spina bifida is still a challenge. A new indirect ultrasound sign of open spina bifida between 11-13 6 weeks of gestation (w.g.) has been recently described. The marker is associated with an absence of intracranial translucency (IT) in the mid-sagittal plane. We present a case report of an open spina bifida detected at 13+2 weeks of gestation with an absent IT. The main ultrasound characteristics of normal and absent IT are described. In addition, the diagnostic role of three-dimensional (3D) transvaginal ultrasound is also discussed.

[Hormonal treatment of recurrent spontaneous abortions].

A retrospective study with 79 pregnant women was conducted. All of them were diagnosed as spontaneous abortion. The patients were separated in two group and the women have been treated in two schemes--51%--Utrogestan and 49%--Utrogestan and Profasi. The medication was applied only into the first trimester of the pregnancy. The duration of the therapy was 15.0 +/- 12.34 days. The mean gestational age in this study was 7.6 +/- 3.0 gestational weeks. Women with a first pregnancy and spontaneous abortion were excluded from the study. The number of this hormonal treated pregnancy was 2.84 +/- 1.13. 10.2% of the followed women had 3 and more than 3 miscarriages. The followed group of women was historically and clinically heterogenic. For that reason we think that many other factors could play a role in the optimum outcome of this pregnancy. The criteria for positive result we accepted the vital embryo/fetus on the time of dehospitalization. From these pregnancy only 3 terminated with miscarriage--3.79%. The rest of 96.2% went at home with intact pregnancy. The authors try to find a theoretical support for use of micronized progesterone Utrogestan--there could be some changes in the cellular and humoral immunity at repeated abortions, related to the change of the cytokine production. It could be find an ability to realize a readjustment of the endocrine system of the mother and to control the immune reaction in the fetoplacental unit.

Conduction block--the diagnostic value in the early stage of Guillain-Barre syndrome.

Immune-mediated segmental demyelination is the basic pathomorphological substrate of the Guillain-Barre syndrome (GBS). The aim of the study is to determine the diagnostic value of the conduction block in the early stage of GBS, as well as its changes during of the development of the disease. Sixteen patients with GBS were examined. Electroneurography (motor nerve conduction studies) was performed at interval from the third day of the onset till the first year. Partial CB in the early stage of the disease (range 0-15 days) was registered in 81,2% of the patients. In demyelinating forms of GBS partial CB was determined in 61% of the investigated nerves. It is the most often observed in peroneal nerves, followed by tibial, ulnar and median nerves in the same order. The maximal reduction of the amplitude of the CMAP (maximal CB) was registered before the 30th day from the onset of the disease with following recovery on the sixth month and first year. Partial CB is more often observed in the early phase of GBS, when it could be the only sign of demyelination. When patients reached a clinical plateau, progressive slowing of motor nerve conduction and increasing CB were registered. Proximal CB was revealed more often than distal CB, because of the typical initial localization of the process. In the early phase of GBS, proximal CB is most often found in lower limbs (in peroneal nerve, followed by tibial nerve). In patients with axonal damage, CB was more severe than in demyelinating group. Partial CB is an important diagnostic criterion for segmental demyelination, which helps for confirming the diagnosis of early GBS, when conduction velocity and other electrodiagnostic criteria for demyelination are normal.

Preconcentration of trace elements on a support impregnated with sodium diethyldithiocarbamate prior to their determination by inductively coupled plasma-atomic emission spectrometry.

A procedure is developed for determination of As, Co, Se, Cr, Pb, Zn, Cu, Mn, Cd, Sb, and Sn in water by ICP-AES analysis of alcohol eluates after pre-concentration of the samples. The pre-concentration is performed on a sodium diethyldithiocarbamate supported soft polyurethane foam. The sorbed elements are subsequently eluted with 1-propanol and the alcohol eluates are analysed by ICP-AES. A eight-fold concentration is achieved. An increased sensitivity in the analysis of propanol-water (30:70, v/v) solution is established as compared with aqueous solutions. The strongest effect is observed for As, Se, Pb, Cr, Sn, and Cd-increasing is more than twice. For other elements the matrix influence is by a factor of 1.45 (Cu), 1.36 (Sb), 2.08 (Zn). The method is applied to the analysis of natural water samples.

["Siphon" structure of the digestive system and a method for "siphon" one-stage terminal lateral small-to-large intestine anastomosis with invagination]. / "Sifonnoe" stroenie pishchevaritelnogo kanala i sposob formirovaniia "sifonnogo" odnoétazhnogo invaginatsionnogo terminolateralnogo tonko-tolstokishechnogo anastomoza.

The authors have suggested a hypothesis according to which the alimentary canal consists of the separate autonomous S-shaped functional structures possessing the antireflux and sphincter-like properties. The principle mentioned was used in 9 patients who had a "siphon" one-story invagination small-to-large intestinal anastomosis been created.

[A modification of the classic supraduodenal side-to-side choledochoduodenal anastomosis]. / Vurkhu edna modifikatsiia na klasicheskata supraduodenalna latero-lateralna kholedokho-duodenoanastomoza.

The authors subscribe to the standpoint that a "bile path" passes in biliodigestive anastomoses along the latero-posterior surface of the right hemi-circumference of the hepato-choledochus in the area where the choledocho-digestive anastomoses are constructed. A declivage (to this "bile path" in the hepato-choledochus) supraduodenal latero-lateral choledocho-duodeno-anastomosis is suggested. It is realized through latero-posterior choledochotomy and by oblique section of the duodenum in close proximity to its external edge. The stitches of the common bile duct needle are 2-2.5 mm apart from each other and from the end of the choledochotomy orifice and those of the--3-3.5 mm apart from each other and 6-7 mm from the end of the duodenotomy orifice. The sutures pass totally through the wall of the common bile duct and serous-muscular-submucosally (mucose-muscular-seriously) thorough the duodenal wall.