The Ubiquitin-Associated and SH3 Domain-Containing Proteins (UBASH3) Family in Mammalian Development and Immune Response.

UBASH3A and UBASH3B are protein families of atypical protein tyrosine phosphatases that function as regulators of various cellular processes during mammalian development. As UBASH3A has only mild phosphatase activity, its regulatory effects are based on the phosphatase-independent mechanisms. On the contrary, UBASH3B has strong phosphatase activity, and the suppression of its receptor signalling is mediated by Syk and Zap-70 kinases. The regulatory functions of UBASH3A and UBASH3B are particularly evident in the lymphoid tissues and kidney development. These tyrosine phosphatases are also known to play key roles in autoimmunity and neoplasms. However, their involvement in mammalian development and its regulatory functions are largely unknown and are discussed in this review.

Comparison of Negative Pressure Wound Therapy (NPWT) and Classical Wet to Moist Dressing (WtM) in the Treatment of Complicated Extremity Wounds in Children.

Treating complicated wounds in the pediatric population using traditional wet to moist wound dressing methods is not always appropriate due to the frequent need to change dressings daily or even a number of times a day, causing distress to the patient. Topical negative pressure is a method that allows for fewer dressings and provides localized benefits, thus accelerating wound healing. The merits of this therapy have been proven in studies on adults, but research on the pediatric population is scarce. Here we intend to present the results of negative pressure wound therapy (NPWT) on 34 pediatric patients (study group) and compare them with 24 patients (control group) treated with the traditional wet to moist dressing for complicated wounds. The results show that topical negative pressure wound therapy is a safe method that downgrades a wound from a complicated to a simple one and allows definitive coverage using a simpler technique with fewer wound dressings. The scars of the patients in the study group exhibited a better result on a visual scar scale. The patients in the control group had a shorter hospital stay. Based on the recorded results, we were able to make treatment recommendations.

How Well Did the Healthcare System Respond to the Healthcare Needs of Older People with and without Dementia during the COVID-19 Pandemic? The Perception of Healthcare Providers and Older People from the SI4CARE Project in the ADRION Region.

One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare facilities, especially for the older population. The aim of the current study was the exploration of the extent to which the healthcare systems responded to the healthcare needs of the older people with or without cognitive impairment and their caregivers in the Adrion/Ionian region. Data were collected through e-questionnaires regarding the adequacy of the healthcare system and were anonymously administered to older individuals and stakeholder providers in the following countries: Slovenia, Italy (Calabria), Croatia, Bosnia and Herzegovina, Greece, Montenegro, and Serbia. Overall, 722 older people and 267 healthcare stakeholders participated in the study. During the COVID-19 pandemic, both healthcare stakeholders and the older population claimed that the healthcare needs of the older people and their caregivers increased dramatically in all countries, especially in Italy (Calabria), Croatia and BiH. According to our results, countries from the Adrion/Ionian regions faced significant challenges to adjust to the special needs of the older people during the COVID-19 pandemic, which was possibly due to limited accessibility opportunities to healthcare facilities. These results highlight the need for the development of alternative ways of providing medical assistance and supervision when in-person care is not possible.

ATTITUDES TOWARDS AND HABITS IN ORAL HEALTH OF ADOLESCENTS IN HERZEGOVINA.

The aim of the study was to determine attitudes towards and habits in oral health of adolescents in Herzegovina, as well as to evaluate the possible differences in habits among individuals of different adolescent categories. The study included 120 participants (35 male and 85 female) divided into three adolescent categories, as follows: early (11-14 years of age), middle (15-18 years) and late (19-21 years) adolescence, from the Herzegovina-Neretva Canton, who presented for dental examination. All participants completed the socio-demographic questionnaire and standardized Hiroshima University Dental Behavioral Inventory (HU-DBI). The answers provided by study adolescents in the HU-DBI showed statistically significant differences among particular age groups, i.e. between early and middle adolescence in items 7 (p=0.046) and 15 (p=0.007); between middle and late adolescence in items 8 (p=0.021), 11 (p=0.04) and 12 (p=0.027); and between middle and late adolescence in item 11 (p=0.032). Respondents in middle adolescence had poorer oral hygiene attitudes than those in early and late adolescence. In order to improve the oral hygiene habits of adolescents in Herzegovina, it is necessary to put emphasis on continuous education about oral hygiene habits during their secondary education.

GREB1L, CRELD2 and ITGA10 expression in the human developmental and postnatal kidneys: an immunohistochemical study.

BACKGROUND: Aim of our study is to provide an insight into the genetic expression landscape of GREB1L, ITGA10 and CRELD2 which are important in human genitourinary tract development which might help elucidate the critical stages for the onset of kidney anomalies. METHODS: Morphological parameters were analyzed using immunohistochemistry on human foetal (13-38 w) and postnatal (1.5 and 7.5y) human kidney samples. RESULTS: GREB1L marker had a strong intensity and the highest rate in proximal tubules (PTC) of 1.5 years' kidney (90.25%). In the distal tubules (DCT) there were statistically significant differences in 13 w, 15 w, 16 w, 21 w, 38 w and 7.5y regarding 1.5y (Kruskal-Wallis test, p < 0.001). There was significantly more GREB1L in the glomeruli at 21 w and 38 w in regard to all other stages (Kruskal-Wallis test, p < 0.01). ITGA10 staining intensity was strongest in PCT with the highest rate in 13 w (92.75%), while the lowest rate was found in glomeruli and DCT (Kruskal-Wallis test, p < 0.001). CRELD2 had the strongest staining intensity in PCT with the highest rate in 13 w and 1.5y (92.25%) and lowest in the glomeruli of 7.5 years (24.3 %). In DCT there were statistically significant differences in CRELD2 positive cells in 13 w, 15 w, 16 w, 21 w, 38 w and 7.5y regarding 1.5y (Kruskal-Wallis test, p < 0.01). ITGA10 and CRELD2 co-localised in the postnatal period in DCT. CONCLUSION: High kidney expressions of GREB1L, ITGA10 and CRELD2 even in the postnatal period implicate their importance not only for the onset of CAKUT in the case of their mutation but also for maintenance of kidney homeostasis.

Immunohistochemical expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the normal human kidney development.

AIM: Present study analyses the co-localisation of RIP5 with FGFR1, FGFR2 and HIP2 in the developing kidney, as RIP5 is a major determinant of urinary tract development, downstream of FGF-signaling. METHODS: Paraffin embedded human kidney tissues of 16 conceptuses between the 6th-22th developmental week were analysed using double-immunofluorescence method with RIP5/FGFR1/FGFR2 and HIP2 markers. Quantification of positive cells were performed using Kruskal-Wallis test. RESULTS: In the 6th week of kidney development RIP5 (89.6%) and HIP2 (39.6%) are strongly expressed in the metanephric mesenchyme. FGFR1 shows moderate/strong expression in the developing nephrons (87.3%) and collecting ducts (70.5%) (p < 0.05). RIP5/FGFR1 co-localized at the marginal zone and the ureteric bud with predominant FGFR1 expression. FGFR2 (26.1%) shows similar expression pattern as FGFR1 (70.5%) in the same kidney structures. RIP5/FGFR2 co-localized at the marginal zone and the collecting ducts (predominant expression of FGFR2). HIP2 is strongly expressed in collecting ducts (96.7%), and co-localized with RIP5. In 10th week, RIP5 expression decrease (74.2%), while the pattern of expression of RIP5 and FGFR1 in collecting ducts (33.4% and 91.9%) and developing nephrons (21.9% and 32.4%) (p < 0.05) is similar to that in the 6th developmental week. Ureter is moderately expressing RIP5 while FGFR1 is strongly expressed in the ureteric wall. FGFR2 is strongly expressed in the collecting ducts (84.3%) and ureter. HIP2 have 81.1% positive cells in the collecting duct. RIP5/FGFR1 co-localize in collecting ducts and Henley's loop. CONCLUSIONS: The expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the human kidney development might indicate their important roles in metanephric development and ureteric muscle layer differentiation through FGF signaling pathways.

Expression and localization of DAB1 and Reelin during normal human kidney development.

AIM: To explore the spatial and temporal expression patterns of DAB1 and Reelin in the developing and postnatal healthy human kidneys as potential determinants of kidney development. METHODS: Paraffin-embedded fetal kidney tissue between the 13/14th and 38th developmental weeks (dw) and postnatal tissue at 1.5 and 7 years were stained with DAB1 and Reelin antibodies by double immunofluorescence. RESULTS: During the fetal kidney development and postnatal period, DAB1 and Reelin showed specific spatial expression pattern and diverse fluorescence intensity. During the fetal period, DAB1 was strongly expressed in the distal convoluted tubules (DCT), with strong reactivity, and diversely in the proximal convoluted tubules (PCT) and glomeruli. In the postnatal period, DAB1 expression decreased. The strongest Reelin expression in early fetal stages was observed in the PCT. In the postnatal period, Reelin expression decreased dramatically in all observed structures. These two markers were colocalized during early developmental stages, mostly in PCT, DCT, and podocytes. CONCLUSION: The appearance of DAB1 and Reelin during fetal kidney development confirms their potential significant role in the formation of kidney structure or function. High DAB1 expression in the DCT implies its regulatory role in tubular formation or function maintenance during development. Reelin was highly expressed in human kidneys at early fetal stages, mostly in the PCT, while at later fetal stages and postnatal period its expression decreased.

Glomeruli from patients with nephrin mutations show increased number of ciliated and poorly differentiated podocytes.

BACKGROUND: Podocytes are postmitotic, highly specialized cells which maintain the glomerular filtration barrier (GFB). Their injury is characterized by foot processes effacement and change in protein expression leading to proteinuria and end-stage kidney disease. METHODS: Our study focuses on the morphological and immunohistochemical changes of human podocytes during normal development and postnatal period, compared to congenital nephrotic syndrome of the Finnish type (CNF). Kidney tissues taken from 17 human conceptuses 8th-38th weeks old, two healthy and three CNF kidneys were embedded in paraffin for immunohistochemical or double immunofluorescence methods, or were embedded in resin for electron microscopy. Paraffin sections were stained with markers for proliferation (Ki-67), proteins nephrin and nestin, and alpha-tubulin. Quantification of positive cells were performed using Mann Whitney and Kruskal-Wallis test. RESULTS: Tissue analysis showed that proliferation of podocytes gradually decreased during development and disappeared in postnatal period. Decrease in number of ciliated glomerular cells and visceral podocytes (from 47% to 3%), and parietal epithelial cells (from 32% to 7%) characterized normal development. Nestin and nephrin co-expressed in developing podocytes in different cellular compartments. During development, nephrin expression increased (from 17% to 75%) and postnatally changed its pattern, while nestin positive glomerular cells decreased from 98% to 40%. CNF glomeruli displayed increased number of immature ciliated podocytes (6%) and parietal epithelial cells (9%). CONCLUSION: Changes in cytoplasmic alpha-tubulin expression and reduced nephrin expression (20%) indicating association of incomplete podocyte maturation with failure of GFB function and appearance of prenatal proteinuria in CNF patients.

Expression of Epithelial and Mesenchymal Differentiation Markers in the Early Human Gonadal Development.

Expressions of cytokeratin 8 (CK8), vimentin, nestin, and alpha-smooth-muscle-actin (alpha-SMA) were analyzed in the developing gonads of 12, 5-9 week old (W) human conceptuses by immunohistochemistry and immunofluorescence. During the investigated period, the number of CK8 positive cells increased from 56% to 92% in the gonadal surface epithelium, from 50% to 60% in the stroma, and from 23% to 42% in the medulla. In the early fetal period, the cell expression of CK8 increased in all gonadal parts, whereas primordial germ cells (PGC) remained negative. The expression of vimentin increased in the gonad stroma (gs) from 73% to 88%, and in the surface epithelium from 18% to 97% until ninth W. The medulla had the highest expression of vimentin in the seventh to eighth W (93%). Vimentin and CK8 colocalized in the somatic cells, while some PGCs showed vimentin expression only. Initially, nestin was positive in the gonad surface epithelium (8%) and stroma (52%), however during further development it decreased to 1% and 33%, respectively. In the early fetal period, the nestin positive cells decreased from 44% to 31% in the gonad medulla. Alpha-SMA was positive only in the blood vessels and mesonephros. The described pattern of expression of intermediate filaments (IF) in developing human gonads suggests their role in the control of PGC apoptosis, early differentiation of gs cells and cell migration. Both epithelial and mesenchymal origins of follicular cells and possible epithelial-to-mesenchymal transition of somatic cells is proposed. Lastly, IF intensity expression varies depending on the cell type and developmental period analyzed. Anat Rec, 300:1315-1326, 2017. © 2017 Wiley Periodicals, Inc.

Recent diagnostic and therapeutic approaches to prenatally and perinatally diagnosed hydronephrosis and their implementation in the University Clinical Hospital Mostar.

A shift of the diagnostics of urological malformations towards the fetal age by means of ultrasound, especially hydronephrosis which, apart from reflux, is the most frequent developmental urological disorder, opened many dilemmas and debates. In the course of more than three decades the application of this diagnostic approach to the problem of hydrone- phrosis became a routine clinical practice in all modern clinics. In this paper we present the problems related to this diagnostic method and its delayed application in the Mostar University Clinical Hospital. Along with the exposition of a general approach to the problem of hydronephrosis we briefly present our modest collection of cases which points to the most recent trend of a vigorous medical development in this region, despite unfavorable overall conditions which prevailed so far. The observation included 56 children with prenatal, perinatal and early age determination of pyelon dilatation by means of ultrasonic exploration who were treated surgically. Of this number 32 (57.14%) were male, and 24 (42.86%) female children. Of the observed patients 56 had unilateral and 6 had bilateral pyelon dilatation so that 62 kidneys in all were observed and treated. The dilatation was determined prenatally in 24 (38.7%) out of 62 kidneys observed in all, in 7 (11.29%) the disorder was observed perinatally and in remaining 31 cases (49.9%) it manifested during early childhood, school age, even at the age of pre-puberty. Of the children with prenatally and perinatally determined dilatation, in 14 (45.16%) out of 31 (100.0%) observed kidneys the ap radius of the dilated pyelon was between 10-15 mm, and in 17 (54.84%) more than 15 mm. Along with other examinations (MAG3 and DMSA) the patients were followed-up by ultrasonic exploration of the observed kidney for 6 to 30 (average 18) months after postnatal diagnosis; the ultrasonic exploration was repeated in intervals of 6 months. Within 12 months of birth surgical intervention on the pyeloureteral junction was done on all 17 kidneys with an ap radius of the pyelon greater than 15 mm, as well as on 4 kidneys in which ap radius was between 10 and 15 mm. In other 10 kidneys with prenatally and perinatally determined ap radius of 10 to 15 mm the follow-up period was 25 to 30 months (average 275). As the examinations (ultrasound, MAG3 and DMSA) even after this period showed no signs of regression of the dilatation, nor an improvement in patency this provided an indication for surgical intervention with the aim of establishing a normal flow across the pyeloureteral junction. Antibiotic prophylaxis was not applied systematically, but in a targeted manner if the uroinfection was confirmed clinically and in the lab. Through the presentation of cases we demonstrate the relationship of earlier and more recent procedures in the treatment of hydronephrosis in the gravitational area of the Mostar University Clinical Hospital. The fact that some children were subjected to surgical treatment due to hydronephrosis at the time of pre-puberty reflects earlier views on this clinical entity. The successfulness of surgical treatment of hydronephrosis in the observed patients is complete and comparable to medically more developed environments, and our diagnostic capabilities are getting close to that level too. We specially wish to stress the recent introduction of ultrasonic examination of pregnant women and foetus in the third trimester with the aim of an early detection of anomalies and malformations of the urotract as an indicator of a marked medical devel- opment. On the global level there are still inconclusive and opposing opinions on this subject, as is seen in recent literature. The controversies relate to the diagnostics as well as to therapy.

The advantages of end-to-side arteriovenous anastomosis over the other two types of arteriovenous anastomosis in dialysis patients.

The functional duration of vascular access in dialysis patients depends on the emergence of threatening complications. Discussions are constantly being held in an attempt to discover their causality and decrease their emergence. In 260 patients undergoing haemodialysis, we have studied the potential existence of a cause-and-effect relation between the emergence of complications in the vascular access and the applied type of arteriovenous (av.) anastomosis in the arteriovenous (AV) fistula. We have observed the incidence of all complications, both that of the thrombosis incidence as well as the primary and secondary fistula patency (survival). The complications--The examinees with the end-to-end anastomosis showed the incidence of 8.08%, 6.15% of the patients with the end-to-side anastomosis and 7.31% of the patients with the side-to-side anastomosis. The differences regarding incidences are statistically significant (chi2-test = 29.25; P = 0.0001). Thrombosis--it has been found that thrombosis was the most frequent complication developing in 30.00% patients with the end-to-end av. anastomosis, in 2.31% patients with end-to-side av. anastomosis and in 5.56% patients with side-to-side av. anastomosis. The difference between the highest and the lowest assessment is 27.69%, and it is statistically relevant (chi2-test = 33.920; P = 0.0001). The primary patency (primary survival): within a 6-month interval following the establishment of vascular access, the first complications arose in 62.50% of patients with end-to-end av. anastomosis, 10.76% in those with end-to-side av. anastomosis and 18.88% in those with side-to-side av. anastomosis. The difference between the highest and the lowest assessment is 51.74%, which is statistically significant (chi2-test = 49.009; P = 0.0001). The secondary patency: 24 months subsequent to the establishment of vascular access, the AV-fistula was still functional in 52.50% of the patients with end-to-end av. anastomosis, 89.23% in those with end-to-side av. anastomosis and 81.11% in those with side-to-side av. anastomosis. The difference between the highest and the lowest assessment is 36.73%, which is also statistically significant (chi2-test = 26.579; P = 0.0001). According to our research, the end--to-side type of av. anastomosis in vascular access provides better results both in relation to the duration as well as the maintenance of the functionality of the Av-fistula and in the lower incidence of the complications than the other types, and hence it shows a definite advantage.

Snodgrass' urethroplasty in hypospadias surgery in Clinical Hospital Mostar--preliminary report.

Amongst the various methods of reconstructing the hypospadic urethra such as the MAGPI, Mathieu's and Preputial island flap urethroplasty method and the Snodgrass method, the latter is being used more frequently nowadays in patients with the urethral meatus located in the proximity of the penis. In the Pediatric ward at Mostar Clinical Hospital, we have recently adopted the Snodgrass method when reconstructing the hypospadic urethra. We herewith present our research regarding the successful results in adopting the aforementioned method. Success was evaluated according to the frequency of post-operative complications, as well as the patients' satisfaction with the functional and the cosmetic result of the urethra reconstruction. The conclusions relating to our research result in an addition basis from which to evaluate whether the Snodgrass method should receive privileged preference in future operative treatment of the hypospadias over others methods, as can be seen from our research.

Burkitt's lymphoma in the boy: infiltration in the stomach, colon and the retroperitoneum--ileocecal invagination.

A 4-year-old boy was hospitalised because showing signs of weakness, slight pain in the abdomen and while urinating. The symptoms occurred 7 days before hospitalisation. The boy did not vomit, nor did he have the urge to vomit, the defecation was regular showing no traces of blood. The physical visit a soft and painless tumefaction was confirmed ileocecally. The echography tests and the computed tomography suggested invagination, not excluding the second substrate. Barium enema showed irreductible invagination. The operative test showed that it was about the ileocolic invagination with extreme thickening of the cecum, the ascedental colon, the intestine and the retroperitoneum walls. A resection of the small intestine and a ileocolic anastomosis was performed. The pathohistological test shows the primar abdominal Burkitt's lymphoma. In spite of the subsequent therapy the boy dies three weeks after the first symptoms' manifestation. We, herewith, suggest at the importance of the echography analysis when diagnosing the Burkitt's tumor and give advantage to this analysis against the computerized tomography. We also point at the huge level of malignancy of the Burkitt's tumor in this boy.

Cerebrovascular insult hospital cases in the Clinical Hospital Mostar (Bosnia and Herzegovina) from 1999 to 2003--an example of an institutional register.

The analysis of a cerebro-vascular insult hospitalized cases in the Clinical Hospital Mostar as a retrospective epidemiological study was done in the Clinical Hospital Mostar for the period from 1999 to 2003. The major source of data was medical documentation of this hospital (an institutional register), the only hospital for the treatments of 457,491 inhabitants who gravitate by a health insurance for the treatment in this hospital. The study included a total of 1,555 cerebro-vascular insult cases treated in the Clinical Hospital Mostar Among them 727 (46.8%) were male patients, while 828 (53.2%) cases were female. The majority of the cases were above 50 years of life. Majority of treated female patients were older than 61 (45.6% of all cases), as well as among male patients (31.3%). The least number of cases was under 41 years in both groups (1.2%). Prevalence of risk factors was 2,035 cases (74%). During the same period risk factors research for entire Federation of Bosnia and Herzegovina (FBiH) was performed on the sample of 2,750 national insurance holders, out of which 852 gravitate for treatment in CB Mostar. Out of them 1.7% was found to suffer of cerebro vascular insult.

Acute coronary syndrome frequency in western Herzegovina over the fifteen year period (1987-2001).

All patients who suffered from the acute coronary syndrome in western Herzegovina over the fifteen year period (1987-2001) are included in this retrospective epidemiological study. The population that was undertaken by the study is relative stabile and did not emigrate during the war period. The study compared the time before the war (1987-1991), during the war (1992-1996) and after the war (1997-2001). The data were acquired from the archives of the patients of the Mostar hospital and Clinical hospital Split during the war period. A total of 2022 acute coronary syndrome patients were found, 1305 men and 717 women. More patients were treated during the war compared to the time before the war for both male and female patients (p<0.0005). During the after-war period the number of treated patients was greater (p< 0.0005) compared to the war-time for both sexes. The comparison of the after-war period and the pre-war period reveals a statistically significant difference as the number of treated patients (male and female) is larger in the after-war period. The number of patient who are 65 years old and older than that is greater, and that is statistically significant (p= 0.0005.). We can conclude that the stress caused by the war and other factors have influenced a larger number of treated patients of acute coronary syndrome. Therefore, further epidemiological researches of acute coronary syndrome with the accent on prevention and treatment are needed.