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Type-A γ-aminobutyric acid receptors (GABA(A)Rs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits( 1,2 ) and are modulated by essential medicines including general anaesthetics and benzodiazepines( 3 ). Human GABA(A)R subunits are encoded by 19 paralogous genes which can, in theory, give rise to 495,235 receptor types. Yet, the principles governing the formation of pentamers, the permutational landscape of receptors that may emerge from a subunit set and the impact this has on GABA-ergic signalling remain largely unknown. Here, we use cryogenic electron microscopy (cryo-EM) to determine structures of extrasynaptic GABA(A)R assembled from α4, β3 and δ subunits, and their counterparts incorporating γ2 instead of δ subunits. In each case we could identify two receptor subtypes with distinct stoichiometries and arrangements, all four differing from those previously observed for synaptic, α1-containing receptors( 4–7 ). This, in turn, affects receptor responses to physiological and synthetic modulators by creating or eliminating ligand binding sites at subunit interfaces. We provide structural and functional evidence that selected GABA(A)R arrangements can act as coincidence detectors, simultaneously responding to two neurotransmitters, GABA and histamine. Using assembly simulations and single-cell RNA sequencing data( 8,9 ), we calculate upper bounds for receptor diversity in recombinant systems and in vivo. We propose that differential assembly is a pervasive mechanism for regulating the physiology and pharmacology of GABA(A)Rs.

Cjelokupni kralježnički sustav nam omogućuje kretanje te služi kao potporanj trupu pri raznim aktivnostima. Pri određenim aktivnostima (poput teškog fizičkog rada) se mogu pojaviti preopterećenja kralježničkog stupa koja mogu uzrokuju rupture na samim kralježničkim diskovima. Najčešće pogođeno područje degenerativnim promjenama su kralježnički diskovi lumbalnog dijela kralježnice, točnije, lumbalni kralježnički diskovi L4-L5 te L5-S1, jer nose najveću težinu te su uglavnom izloženi značajnom naprezanju i pritisku. Cilj ovog rada je prikazati 3D model umjetnog L5-S1 kralježničkog diska izrađenog u softverskom programu Solidworks, prema proizvoljnim geometrijskim karakteristikama te poznatim geometrijskim karakteristikama iz literature, koji bi poslužio kao moguća zamjena L5-S1 kralježničkog diska u slučaju težih degenerativnih promjena te za analizu naprezanja samoga 3D modela metodom konačnih elemenata u softverskom paketu Abaqus. Pritom se daje detaljan opis izbora materijala umjetnog kralježničkog diska u svrhu postizanja što bolje biokompatibilnosti s ljudskim tijelom kako bi se spriječilo odbacivanje implantata. The entire spinal system allows us to move and serves as a support for the body hull in various activities. With certain activities (such as heavy physical work), spinal column overloads occur which can cause ruptures on the spinal discs themselves. The most frequently affected area by degenerative changes are the spinal discs of the lumbar part of the spine, namely, the lumbar spinal discs L4-L5 and L5-S1, as they carry the greatest weight and are mainly exposed to significant stress and pressure. The aim of this thesis is to present a 3D model of an artificial L5-S1 spinal disc made in the Solidworks software program, according to the arbitrary geometric characteristics and known geometric characteristics from the literature, which would serve as a possible replacement of the L5-S1 spinal disc in case of severe degenerative changes and the stress analysis of the 3D model itself by the finite element method in the Abaqus software package. In doing so, a detailed description is given about the choice of artificial spinal disc materials in order to achieve the best possible biocompatibility with the human body and thus prevent rejection of implants.

The three-dimensional positions of atoms in protein molecules define their structure and the roles they perform in biological processes. The more precisely atomic coordinates are determined, the more chemical information can be derived and the more mechanistic insights into protein function may be inferred. With breakthroughs in electron detection and image processing technology, electron cryo-microscopy (cryo-EM) single-particle analysis has yielded protein structures with increasing levels of detail in recent years(1,2). However, obtaining cryo-EM reconstructions with sufficient resolution to visualise individual atoms in proteins has thus far been elusive. Here, we show that using a new electron source, energy filter and camera, we obtained a 1.7 Å resolution cryo-EM reconstruction for a human membrane protein, the β3 GABA(A) receptor homopentamer(3). Such maps allow a detailed understanding of small molecule coordination, visualisation of solvent molecules and alternative conformations for multiple amino acids, as well as unambiguous building of ordered acidic side chains and glycans. Applied to mouse apoferritin, our strategy led to a 1.22 Å resolution reconstruction that, for the first time, offers a genuine atomic resolution view of a protein molecule using single particle cryo-EM. Moreover, the scattering potential from many hydrogen atoms can be visualised in difference maps, allowing a direct analysis of hydrogen bonding networks. The technological advances described here, combined with further approaches to accelerate data acquisition and improve sample quality, provide a route towards routine application of cryo-EM in high-throughput screening of small molecule modulators and structure-based drug discovery.

Guidelines for cardiovascular drug therapy recommend monitoring serum digoxin concentration (SDC) in patients receiving digoxin treatment, especially those with renal dysfunction and hypokalemia. However, only a few studies have reported the prevalence of SDC monitoring and laboratory testing in clinical practice. Therefore, the aim of this study was to describe the frequency of SDC monitoring and laboratory testing in digoxin users and to assess the association between SDC monitoring and patient characteristics. We used the Japanese insurance claims data covering approximately 1.7 million patients aged 20-74 years between January 1, 2005 and March 31, 2014. All patients who had at least one prescription for digoxin were included. The frequency of SDC and laboratory tests was calculated and the association between patient characteristics and SDC monitoring was assessed using logistic regression analysis. A total of 98867 prescriptions of digoxin were issued to 3458 patients between 2005 and 2014. The annual mean frequencies of monitoring SDC, serum potassium level and serum creatinine level and of recording electrocardiograms was 16.8, 34.8, 38.7, and 24.1%, respectively. Atrial fibrillation, chronic heart failure, renal diseases, and use of oral anticoagulants were associated with SDC monitoring. We found the frequency of SDC monitoring to be relatively low in Japanese clinical practice.

Bacterial infections are associated with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but the mechanism is incompletely understood. In a COPD observational study (NCT01360398), sputum samples were collected monthly at the stable state and exacerbation. Post-hoc analyses of 1307 non-typeable Haemophilus influenzae (NTHi) isolates from 20 patients and 756 Moraxella catarrhalis isolates from 38 patients in one year of follow-up were conducted by multilocus sequence typing (MLST). All isolates came from cultured sputum samples that were analyzed for bacterial species presence, apparition (infection not detected at the preceding visit), or acquisition (first-time infection), with the first study visit as a baseline. Strain apparition or new strain acquisition was analyzed by MLST. The odds ratio (OR) of experiencing an exacerbation vs. stable state was estimated by conditional logistic regression modelling, stratified by patient. The culture results confirmed a significant association with exacerbation only for NTHi species presence (OR 2.28; 95% confidence interval [CI]: 1.12–4.64) and strain apparition (OR 2.38; 95% CI: 1.08–5.27). For M. catarrhalis, although confidence intervals overlapped, the association with exacerbation for first-time species acquisition (OR 5.99; 2.75–13.02) appeared stronger than species presence (OR 3.67; 2.10–6.40), new strain acquisition (OR 2.94; 1.43–6.04), species apparition (OR 4.18; 2.29–7.63), and strain apparition (OR 2.78; 1.42–5.42). This may suggest that previous M. catarrhalis colonization may modify the risk of exacerbation associated with M. catarrhalis infection. The results confirm that NTHi and M. catarrhalis infections are associated with AECOPD but suggest different dynamic mechanisms in triggering exacerbations.

Bioaktivne molekule često sadrže neke zajedničke strukturne motive koji čine okosnicu njihovih molekularnih struktura [1]. Suvremeni putevi u sintezi biomimetskih lijekova koji sadrže neke od najčešćih malih bioaktivnih skeleta ilustriraju potencijal ovih molekula u istraživanjima novih mogućih lijekova. Neki odabrani bioaktivni skeleti bit će dokirani u aktivno mjesto butirilkolinesteraze korištenjem kvantno- mehaničkog dokinga [2, 3]. Sustavna pretraga konfiguracijskog prostora bit će provedena korištenjem kombinatoričkog pretražnog algoritma koji uključuje translacijske i rotacijske stupnjeve slobode. Za svaku generiranu konfiguraciju sustava izračunat će se energija korištenjem PM7 hamiltonijana te će se odrediti svi mogući lokalni minimumi. Za odabrane lokalne minimume optimizirat će se geometrija korištenjem kvantno-mehaničko/kvantno-mehaničkog pristupa unutar ONIOM formalizma te će se odrediti standardne Gibbsove energije vezanja.

The most important interactions of small molecules with cholinesterases were investigated by quantum mechanical docking. A systematic search of the configurational space was conducted using a combinatorial search algorithm [1]. The following degrees of freedom were taken into account: three translational and three rotational degrees of freedom. Small molecules were translated within the active site in steps of 1 Å and rotated with increments of 60°. For every generated configuration electronic energy calculations were performed using the PM7 Hamiltonian and the search for all local minima was carried out [2]. For the selected local minima combined quantum mechanical/quantum mechanical (QM/QM) optimizations were performed and relative standard Gibbs energies of binding were calculated. All quantum chemical calculations were done using the Gaussian 16 program package.

Teaching readiness and capability of teachers’ mirror the quality of students’ achievements. The determination of readiness and capability of teachers particularly in island schools identified the extent of teachers’ competence despite online skill inadequacies amidst the pandemic. The study included a relationship of personal factors that have bearing on teachers’ readiness and capability. Descriptive-correlational research design was used with simple random sampling. One hundred seventy-two (172) teachers provided the needed data. Data were gathered through a researcher-made questionnaire. The statistical tools used were descriptive statistics, t-test and One-Way ANOVA for significant difference and Pearson r for relationship of teaching readiness and level of teachers’ capability. The findings highlighted teachers’ teaching readiness as high particularly in the preparation of instructional materials and average as to technological requirements such as in place internet access, with computers, laptops, other digital gadgets and delivery of students’ academic needs using technology. While the teachers were highly capable in online skills like creating models, guides, online assessment materials and use of articles, videos and infographics. In the new normal class management, teachers demonstrated very high capability in stimulating student’s curiosity in learning by integrating real life situations, detailed modules and providing an engaging environment through oral communication. No significant differences were found on the degree of teaching readiness and level of teachers’ capability when respondents were grouped according to their selected profile. However, teaching readiness has significant bearing on teachers’ online capability.

Biološki sustavi iznimno su kompleksni, što ih istovremeno čini zanimljivima, ali i zahtjevnima za proučavanje. Kako bi objasnili pojedina neočekivana eksperimentalna opažanja, znanstvenici su se okrenuli kvantnoj mehanici i njezinoj potencijalnoj uključenosti u biološke procese. Mnogo je procesa za koje se pretpostavlja da kvantni efekti imaju presudnu ulogu u njihovu odvijanju, poput fotosinteze, magnetorecepcije i olfakcije. Enzimska kataliza iznimno je važna za sve žive sustave na Zemlji, stoga je dan osvrt na potencijalnu ulogu kvantno-mehaničkog tuneliranja u mehanizmu enzimske katalize. Tuneliranje je neobičan kvantni efekt koji omogućuje prolazak čestice kroz klasično zabranjene barijere. S obzirom na sve dokaze i kritike, važnost tuneliranja u enzimima još nije jednoznačno potvrđena. Međutim, nesumnjivo je da će kvantno-biološka istraživanja dovesti do novog razumijevanja i pogleda na život. Biological systems are incredibly complex, and that makes them very interesting, but also very challenging to study. To explain certain unexpected experimental results, scientists have taken quantum mechanics into account, and investigated its potential role in biological processes. There are many processes, including photosynthesis, magnetoreception and olfaction, which are thought to have key contributions from quantum effects. Enzyme catalysis is incredibly important for all living systems on Earth, hence the focus of this review is on the potential role of quantum tunnelling in mechanisms of enzyme catalysis. Quantum tunnelling is a peculiar quantum effect that enables a particle to pass through classically forbidden barriers. Considering all of the evidence and critiques, the importance of quantum tunnelling in enzymes still hasn’t been unambiguously confirmed. Nonetheless, there is no doubt that the research made in the growing field of quantum biology will lead to a new understanding of life.

The extent to which production agriculture adopts technologies that mitigate the impacts of climate change on crop yields will impact our ability to feed nine billion people by the year 2050. For many risk-averse farmers in developed countries, government business risk management programs help manage yield risks under a changing climate. I use a neural network to predict average county corn yields for Ontario and Iowa over the years 2022-2084 under various climate change scenarios. I also estimate rates of technological change, yield resiliency, and crop insurance premium rates in these predicted yield distributions using a normal mixture model. In both Ontario and Iowa, predicted yield distributions shift rightward and exhibit component divergence over time across climate scenarios. Strictly positive rates of technological change and variable Ontario county AgriInsurance premium rates suggest that funding AgriInsurance into the future may require a larger share of taxpayer dollars. Ontario Ministry of Agriculture, Food, and Rural Affairs; The Ivey Foundation; Professor Alan Ker at the Department of Food, Agricultural, and Resource Economics, Managing Editor of the Canadian Journal of Agricultural Economics, Ontario Agricultural College Research Chair in Agricultural Risk and Policy, and Director of the Institute of Food and Agricultural Policy at the University of Guelph

The public health burden of travel related diseases (TRDs) remains significant despite the fact that most can be avoided, particularly with the assistance of local tourist handlers such as Safari Tour Operators' (STOs). The STO's are the immediate close contact with tourist groups, and yet their perspectives regarding provision of travel health advice are unknown in Uganda. This study was conducted to determine the level of knowledge, attitude, and practices of STOs regarding TRDs in Uganda.A cross sectional study was carried out among selected STOs in Kampala and Wakiso Districts using self-administered questionnaires.The overall level of knowledge about travel health information was inadequate. Although 77.5% of the STOs were aware of some TRDs, the availability of travel health information or database in their organisations was not observed. Knowledge of the current TRDs in Uganda among the STOs was very low, with a few individuals mentioning yellow fever (9.7%), malaria (9.2%), cholera (9.2%), and HIV/AIDs (8.9%). Knowledge related to the sources of the travel health information was also low, with STOs (19.1%) and travel health clinics (14.9%) being mentioned as the main sources. The STOs had mostly positive attitude towards provision of travel health advice related to travellers, and all agreed that STOs should play a big role in the provision of travel health advice. First Aid and simple treatment options were mentioned as practices that STOs conducted to keep the travellers safe.While the STOs are motivated to do the right thing and provide their clients with sound travel health advice, they have a limited awareness of the actual TRDs in Uganda. The STOs must be educated on pertinent travel health advice, and intra-travel disease and injury management. The responsible government and non-governmental entities in Uganda need to develop educational materials emphasising the relevance of travel health advice.

Nanobodies are popular and versatile tools for structural biology. They have a compact single immunoglobulin domain organization, bind target proteins with high affinities while reducing their conformational heterogeneity and stabilize multi-protein complexes. Here we demonstrate that engineered nanobodies can also help overcome two major obstacles that limit the resolution of single-particle cryo-electron microscopy reconstructions: particle size and preferential orientation at the water-air interfaces. We have developed and characterized constructs, termed megabodies, by grafting nanobodies onto selected protein scaffolds to increase their molecular weight while retaining the full antigen-binding specificity and affinity. We show that the megabody design principles are applicable to different scaffold proteins and recognition domains of compatible geometries and are amenable for efficient selection from yeast display libraries. Moreover, we demonstrate that megabodies can be used to obtain three-dimensional reconstructions for membrane proteins that suffer from severe preferential orientation or are otherwise too small to allow accurate particle alignment.

38th European Photovoltaic Solar Energy Conference and Exhibition; 467-470, The power conversion efficiencies (PCE) of Cu(In,Ga)Se2 (CIGS) cells on lab-scale are approaching c-Si cells. The module efficiencies, on the other hand, are considerably lower.[1], [2] Large-area modules show reduced fill factors and power conversion efficiencies. This so-called cell to module efficiency gap exists for all PV technologies. However, the difference in efficiency for CIGS cells modules is considerably higher than for the more mature Si-technology. This efficiency gap is mainly ascribed to the laterally spread electric defects due to non-uniformities in the materials' properties and the longer current paths over the larger area.[3]

The three-dimensional positions of atoms in protein molecules define their structure and provide mechanistic insights into the roles they perform in complex biological processes. The more precisely atomic coordinates are determined, the more chemical information can be derived and the more knowledge about protein function may be inferred. With breakthroughs in electron detection and image processing technology, electron cryo-microscopy (cryo-EM) single-particle analysis has yielded protein structures with increasing levels of detail in recent years1,2. However, obtaining cryo-EM reconstructions with sufficient resolution to visualise individual atoms in proteins has thus far been elusive. Here, we show that using a new electron source, energy filter and camera, we obtained a 1.7 Å resolution cryo-EM reconstruction for a prototypical human membrane protein, the β3 GABAA receptor homopentamer3. Such maps allow a detailed understanding of small molecule coordination, visualisation of solvent molecules and alternative conformations for multiple amino acids, as well as unambiguous building of ordered acidic side chains and glycans. Applied to mouse apo-ferritin, our strategy led to a 1.2 Å resolution reconstruction that, for the first time, offers a genuine atomic resolution view of a protein molecule using single particle cryo-EM. Moreover, the scattering potential from many hydrogen atoms can be visualised in difference maps, allowing a direct analysis of hydrogen bonding networks. Combination of the technological advances described here with further approaches to accelerate data acquisition and improve sample quality provide a route towards routine application of cryo-EM in high-throughput screening of small molecule modulators and structure-based drug discovery.

Преваленца гојазности и метаболичког синдрома у јувенилној популацији једраматично у порасту и представља јавно-здравствени проблем у целом свету.Гојазност, нарочито висцералног типа, је кључни аспект за појаву метаболичкогсиндрома или појединих његових компоненти у млађој популацији. Оваква патолошкастања доводе до појаве низ компликација као и фактора ризика за настанаккардиоваскуларних обољења и дијабетеса типа II, касније у адултној доби. Циљ овестудије био је да се утврде ефекти програма физичке активности и хипокалоријскеисхране на антропометријске, конституционалне, метаболичке и кардиоваскуларнепараметре код гојазне деце, имајући у виду да је за настанак гојазности управоодговоран животни стил у смислу неадекватне исхране и хипокинезије код младих. Уту сврху креиран је упитник на основу ког смо дoбили увид о животним навикамаиспитаника и закључили да се ради о гојазној јувенилној популацији, са врло малоквалитативног уноса хранљивих материја и физички неактивном у великој мери.Такође присутна је и генетска предиспонираност за кардиоваскуларне и метаболичкеболести, на шта нам указује породична анамнеза. Програм физичке активности идијететског режима, прилагођен узрасној групи испитаника од 11-14 година ± 0.5 год,био је краткорочног карактера у трајању од три месеца. У циљу провере ефектамултидисциплинарног третмана, сви испитивани параметри су мерени у три временскетачке (иницијално, трансверзално и финално мерење). Дескриптивне резултати у светри групе испитиваних параметара показују статистички значајне промене код свихиспитаника у све три временске, као и резултати једнофакторске униваријантне анализеваријансе (ANOVA) за поновљена мерења (one-way repeated measures ANOVA) за Sig.<0,05. Телесна маса и обими трбуха су значајно редуковани као и сви остали параметрициркуларне димензионалности и поткожног масног ткива, исхрањености иконституције. Код физиолошких показатеља метаболичког синдрома такође је дошлодо редукције и позитивних промена. Потврда је добијена мултиваријатном анализомваријансе за поновљена мерења (One-way repeated measures MANOVA) за Sig.дате тестом Wilk’s Lambda, чиме смо потврдили значајан ефекат спроведеног третманавежбања и редуковане исхране, који је изазвао значајне промене у свим посматранимпросторима., Prevalenca gojaznosti i metaboličkog sindroma u juvenilnoj populaciji jedramatično u porastu i predstavlja javno-zdravstveni problem u celom svetu.Gojaznost, naročito visceralnog tipa, je ključni aspekt za pojavu metaboličkogsindroma ili pojedinih njegovih komponenti u mlađoj populaciji. Ovakva patološkastanja dovode do pojave niz komplikacija kao i faktora rizika za nastanakkardiovaskularnih oboljenja i dijabetesa tipa II, kasnije u adultnoj dobi. Cilj ovestudije bio je da se utvrde efekti programa fizičke aktivnosti i hipokalorijskeishrane na antropometrijske, konstitucionalne, metaboličke i kardiovaskularneparametre kod gojazne dece, imajući u vidu da je za nastanak gojaznosti upravoodgovoran životni stil u smislu neadekvatne ishrane i hipokinezije kod mladih. Utu svrhu kreiran je upitnik na osnovu kog smo dobili uvid o životnim navikamaispitanika i zaključili da se radi o gojaznoj juvenilnoj populaciji, sa vrlo malokvalitativnog unosa hranljivih materija i fizički neaktivnom u velikoj meri.Takođe prisutna je i genetska predisponiranost za kardiovaskularne i metaboličkebolesti, na šta nam ukazuje porodična anamneza. Program fizičke aktivnosti idijetetskog režima, prilagođen uzrasnoj grupi ispitanika od 11-14 godina ± 0.5 god,bio je kratkoročnog karaktera u trajanju od tri meseca. U cilju provere efektamultidisciplinarnog tretmana, svi ispitivani parametri su mereni u tri vremensketačke (inicijalno, transverzalno i finalno merenje). Deskriptivne rezultati u svetri grupe ispitivanih parametara pokazuju statistički značajne promene kod svihispitanika u sve tri vremenske, kao i rezultati jednofaktorske univarijantne analizevarijanse (ANOVA) za ponovljena merenja (one-way repeated measures ANOVA) za Sig.<0,05. Telesna masa i obimi trbuha su značajno redukovani kao i svi ostali parametricirkularne dimenzionalnosti i potkožnog masnog tkiva, ishranjenosti ikonstitucije. Kod fizioloških pokazatelja metaboličkog sindroma takođe je došlodo redukcije i pozitivnih promena. Potvrda je dobijena multivarijatnom analizomvarijanse za ponovljena merenja (One-way repeated measures MANOVA) za Sig.date testom Wilk’s Lambda, čime smo potvrdili značajan efekat sprovedenog tretmanavežbanja i redukovane ishrane, koji je izazvao značajne promene u svim posmatranimprostorima., Prevalence of obesity and metabolic syndrome in juvenile population is increasingdramatically and presents a worldwide public health problem. Obesity, the visceral type inparticular, is the key aspect for emergence of metabolic syndrome or some of its individualcomponents in the younger population. Pathological states of this kind lead to development ofa range of complications, as well as, risk factors for emergence of cardiovascular diseases anddiabetes type II, later in adult age. The aim of this study was to determine effects of a programof physical activity and hypocaloric diet on anthropometric, constitutional, metabolic andcardiovascular parameters in obese children, considering that it is lifestyle, namely inadequatediet and lack of movement, which is responsible for emergence of obesity in children. Withthis in mind, we have created a questionnaire which has given us an insight into living habitsof the participants, and we have determined that we are dealing with an obese juvenilepopulation which consumes very little of quality nutritious foods, and which is, to a greatextent, physically inactive. Also, there is a presence of genetic predisposition forcardiovascular and metabolic diseases, which was indicated in family anamnesis. Thephysical activity and diet regime program, adapted to the age group of the participants (11 to14-year-olds ± 0.5 year) was short term in character and it lasted for three months. With theaim of checking the effect of the multidisciplinary treatment, all the tested parameters weremeasured at three points in time (initial, transversal and final measurements). Descriptiveresults in all three groups of the measured parameters indicate statistically significant changesin all the participants, at all three time points, as do the results of one-way repeated measuresANOVA for Sig.< 0,05. Body mass and abdominal circumferences were reducedsignificantly, as were all the other parameters of circulatory dimensions and subcutaneous fat,nourishment and constitution. Reduction and positive changes were also measured inphysiological indicators for metabolic syndrome. The results were confirmed by one-wayrepeated measures MANOVA for Sig.< 0.05, using the Wilk’s Lambda test, through whichwe have confirmed a significant effect of the applied treatment which has caused significantchanges in all the measured parameters.

Početni dio probavnog i djelomično dišnog sustava je usna šupljina. Usna šupljina zajedno sa pripadajućim organima sudjeluje u prvim koracima probave hrane. Oralno zdravlje predstavlja važan dio općeg zdravlja, a uključuje zdravlje cjelokupne usne šupljine odnosno zdravlje zuba, paradontnog tkiva, sluznice i žlijezde slinovnica. Pravilnim provođenjem oralne higijne, korištenjem mehaničkih i kemijskih sredstava onemogućava se sakupljanje plaka i njegova mineralizacija. Kod djece do 3 godine najveći krivac pojavljivanja karijesa, uz nedovoljno i nepravilno održavanje oralne higijene, je bočica. Pravilnom i uravnoteženom prehranom može se utjecati na kvalitetu zuba. Pravilna higijena i redoviti pregledi, pomažu da se zdravlje zuba očuva. Najvažniju ulogu za održavavanje oralne higijene imaju sredstva. Sa oralnom higijenom treba započeti i prije nicanja zuba, koje se provodi pomoću sterilne gaze ili jednokratne navlake za prst. Glavno i neizostavno sredstvo oralne higijene je zubna četkica, koja se koristi za čiščenje zubi, desni i jezika. Dok pasta za zube u kombinaciji sa četkicom imaju najveću ulogu za održavanje oralne higijene. Početno, oralnu higijenu bi trebali provoditi roditelji. Roditelji su ti koji svojim primjerom i poticanjem daju podršku djetetu. The initial part of the digestive and partially respiratory system is the oral cavity. The oral cavity together with the associated organs participates in the first steps of digestion of food. Oral health is an important part of general health, and includes the health of the entire oral cavity, respectively the health of teeth, periodontal tissue, mucous membranes and salivary glands. Proper oral hygiene, the regular use of mechanical and chemical instrumentalities prevents the collection of plaque and its mineralization. In children up to 3 years of age, the biggest culprit for caries, with insufficient and improper maintenance of oral hygiene, is the bottle. Proper and balanced diet can affect the quality of teeth. Proper hygiene and regular check-ups help maintain dental health. Instrumentalities play the most important role in maintaining oral hygiene. Oral hygiene should also be started before the teeth erupt, which is done with sterile gauze or a disposable finger cover. The main and indispensable instrumentality of oral hygiene is a toothbrush, which is used to clean teeth, gums and tongue. While toothpaste in combination with a toothbrush play the biggest role in maintaining oral hygiene. Initially, oral hygiene should be carried out by parents. Parents are those who support the child with their example and encouragement.

Arrestins regulate the signaling of ligand-activated, phosphorylated G-protein-coupled receptors (GPCRs). Different patterns of receptor phosphorylation (phosphorylation barcode) can modulate arrestin conformations, resulting in distinct functional outcomes (for example, desensitization, internalization, and downstream signaling). However, the mechanism of arrestin activation and how distinct receptor phosphorylation patterns could induce different conformational changes on arrestin are not fully understood. We analyzed how each arrestin amino acid contributes to its different conformational states. We identified a conserved structural motif that restricts the mobility of the arrestin finger loop in the inactive state and appears to be regulated by receptor phosphorylation. Distal and proximal receptor phosphorylation sites appear to selectively engage with distinct arrestin structural motifs (that is, micro-locks) to induce different arrestin conformations. These observations suggest a model in which different phosphorylation patterns of the GPCR C terminus can combinatorially modulate the conformation of the finger loop and other phosphorylation-sensitive structural elements to drive distinct arrestin conformation and functional outcomes.

Swimming pools have become major recreation facilities for leisure and sports in cities across the world, but the standard guidelines, particularly in developing countries, are not adhered to because little is known about the contaminants in the pools and the possible health risks involved. This study provides a survey of bacterial quality of water from swimming pools in Kampala. A total of 26 water samples were collected from 13 outdoor swimming pools in Kampala between January and June 2016 and analysed for total aerobic plate count (TPC), Escherichia coli, coliforms, and Salmonella. The heterotrophic bacterial load ranged between 0 and 6.35 × 105 cfu/ml, where 6.35 × 105 cfu/ml was the highest load and 3 × 101 cfu/ml the least. The highest average TPC was 6.19 × 105 cfu/ml and the lowest 5.07 × 103 cfu/ml. 30.8% of the pools had TPC within acceptable limits (≤5 × 102 cfu/ml), whereas 69.2% were highly contaminated and did not conform to the Uganda National Water and Sewerage Corporation standards of recreational water quality for both treated (0 cfu/100 mls) water and untreated (10 cfu/100 mls) water. Although no positive results were yielded for E. coli, coliforms, and Salmonella, TPC represented the presence of heterotrophic bacteria which are often indicated in opportunistic infections.

Introduction:cryptosporidium and giardia are of great one health significance and major cause of protozoan diarrhea in humans and primates; they are found in the faecal matter of animals and humans and also in contaminated water and soil as well. Therefore, we aimed at establishing the prevalence and shedding intensity of faecal cryptosporidium and giardia in the Newly Habituated Mountain Gorillas (NHMG) and Previously Habituated Mountain Gorillas (PHMG) and in selected water sources within the gorilla home ranges in the month of January 2018. Methods:we conducted a cross sectional study in the southern sector of Bwindi Impenetrable National Park where a total of 56 faecal samples from both NHMG (34) and PHMG (22) and 30 water samples were purposively collected. Faecal and water samples were transported in a cooler box at 4ºC to Makerere University Parasitology Laboratory for analysis. The samples were analyzed using modified Ziehl-Neelsen technique and Ether concentration method for cryptosporidium and giardia respectively. Results:the prevalence of cryptosporidium was established as 13 (59.1%), 15 (44.1%) and 7 (23.3%) in PHMG, NHMG and water respectively. The mean concentration of the oocysts per gram was 222±52.9 in PHMG, 174±41.5 in NHMG and 31±13.2 in water. The prevalence of giardia was 3 (13.6%), 4 (11.8%) and 3 (10%) in PHMG, NHMG and water respectively. The mean concentration of the oocysts per gram was 34±19.9 in PHMG, 25±12.4 in NHMG and 5±2.9 in water. There was no significant difference in both the prevalence of cryptosporidium (p>0.05) and giardia (p>0.05) in the PHMG and NHMG. This indicates that there is high risk of cross infection among the gorillas within the forest sharing similar home ranges. Conclusion:the park authorities should ensure that procedures for proper waste disposal while in the forest are properly followed, water drawn for drinking from the forest should be avoided. Further research should be carried out to identify whether the strains of the parasites found in water or other animals in the forest are the same with strains in gorilla dung in order to confirm cross infection.

The aim of this research is to develop a smart wristband system architecture that provides real-time information to users in traffic environment. Users in traffic environment are persons with visual impairment, hearing impairment, and locomotor impairment, elderly, children, and persons without disabilities. The purpose of service is to provide users with accurate and real-time information and raising the level of quality of life. Previous research and solutions have provided information about user needs and demands. Conducted survey defined functionalities of system based on Cloud Computing for the Blind concept which provides 24/7 support for the delivery of services and safety of users. Architecture of the service is designed according to universal design and Ambient Assisted Living concept. With simulation testing and experimental methods based on the Arduino and Raspberry Pi platforms, the work of proposed system is tested in laboratory and real-world environment which proved real-time information delivery to users. Having the ability to notify users in real time will increase the level of autonomy and safety while moving through traffic network.