Acid treatment of POSS-Se results in a hydrophilic red-orange colored solid, which is highly sensitive and selective for the detection of Hg2+ ions in aqueous solutions by visually observing the color change to pale yellow, and to white. Interestingly, POSS-Se has no activity on this detection. This finding is due to the Se–Se formation by acid-treatment and subsequent coordination-induced cleavage upon the addition of Hg2+ ions. The detection behavior can be precisely monitored by a “turn-on” fluorescence phenomenon with the limit of detection (LOD) of 8.48 ppb, comparable to or higher than many reported Hg2+ sensors. Moreover, POSS-Se demonstrates a selective and efficient adsorption of Hg2+ ions with a maximum capacity of 952 mg g–1. The value is higher than most reported adsorbents for Hg2+ ions, typically thiol and/or thioether functional materials, indicating its promise as an efficient adsorbent for the selective removal of Hg2+ ions from industrial wastewater. This work may open up new horizons for the exploration of selenium-containing functional POSS.Developing novel functional polyhedral oligomeric silsesquioxane (POSS) for various applications is highly desirable. Herein we present the first example of a novel selenone-functionalized POSS (POSS-Se) by treating an imidazolium-containing POSS with selenium powder under mild condition. The structure of POSS-Se was characterized by FT-IR,  To, PO43–) . AlthougSelenium, a member of group XVI of the periodic table, is an essential element in the human body with potential antioxidant properties . Seleniu2+) among various other metal ions after acid treatment. The detection process can not only be visualized by observing the color change of acidic POSS-Se, but also be precisely monitored by a “turn-on” fluorescence phenomenon. Moreover, the adsorption behavior of POSS-Se towards Hg2+ ions was investigated and it shows a high adsorption capacity, indicating that it can be utilized as a promising candidate for the removal of Hg2+ ions from aqueous solutions.Herein, we combine the selenone groups with POSS units and present the first example of a selenone-functionalized POSS (POSS-Se) by the direct reaction of an imidazolium-functionalized POSS with selenium powder . The res−1 region on a Bruker TENSOR-27 infrared spectrophotometer . 1H NMR, 13C NMR, and 29Si NMR spectra were measured on a Bruker AVANCE-400 NMR spectrometer  using CDCl3 or d6-DMSO as the solvent and without tetramethylsilane (TMS) as an internal reference. Elemental analyses were conducted using an Elementar vario EL III elemental analyzer . Thermogravimetric analysis (TGA) was performed under N2 using a TA SDTQ600  at a temperature range of room temperature to 600 °C with a heating rate of 10 °C min−1. The concentration of Hg2+ ions was measured by a GBC 923B-model atomic absorption spectrophotometer  or inductively coupled plasma mass spectrometry (ICP-MS) . The fluorescent spectra of the samples were determined with a Hitachi F-7000 fluorescence spectrophotometer  using a monochromated Xe lamp as an excitation source. Unless otherwise noted, all reagents were obtained from commercial suppliers and used without further purification. Octa((4-benzylchloride)ethenyl)silsesquioxane (M-1) was synthesized according to the method described in the previous report . Fourier−1): 3136, 3057, 1606, 1567, 1450, 1419, 1383,1361, 1332, 1295, 1201, 1102, 1017, 883, 741, 659, 614, 548, 470. 1H NMR  δ 9.67 , 7.94 , 7.82 , 7.64 , 7.51 , 7.37 , 6.54 , 5.54 , 3.89 . 13C NMR : δ 149.1, 137.3, 136.6, 129.3, 128.0, 124.4, 122.8, 118.2, 51.7, 36.4. 29Si NMR : δ −73.13.In a three-necked bottle, M-1  and 1-methylimidazole  were dissolved in chloroform (15 mL). After reflux for 24 h, the resulting solution was allowed to cool to room temperature. The precipitate was filtered, washed with chloroform, collected, and dried under vacuum at 70 °C for 6 h. The product M-2 was afforded as a white solid . IR (KBr pellet cm−1): 3125, 3089, 2933, 1678, 1606, 1566, 1510, 1460, 1395, 1357, 1234, 1199, 1122, 830, 760, 712, 668, 564, 453. 1H NMR  δ 7.34 , 7.27 , 7.20 , 6.91 , 6.78 , 6.25 , 5.35 , 3.72 . 13C NMR : δ 156.6, 137.1, 136.2, 128.5, 127.2, 120.3, 118.5, 111.8, 109.7, 52.9, 37.4. 29Si NMR : δ −79.48. Anal. Calcd for C104H104N4Se8O12Si8: C, 47.56; H, 3.99; N, 8.53. Found: C, 46.79; H, 4.09; N, 8.46. In a three-necked bottle, M-2  was dissolved in methanol (30 mL). Potassium carbonate  and selenium powder  were added and the reaction mixture was stirred at room temperature for 48 h. The crude product was obtained after filtration and evaporating the solvent. Then 50 mL of water was poured into the crude product and the white solid was precipitated from the aqueous phase. The precipitation was filtered and washed with water. The product POSS-Se was dried under vacuum at 70°C for 6 h and afforded as a white solid . IR  was added to 1.0 M HCl (40 mL) and held for 12 h at room temperature. The precipitate was retrieved by centrifugation, washed by water and dried under vacuum at 70 °C for 6 h. POSS-Se (HCl) was afforded as a red-orange solid.Before the detection of Hg2+ by POSS-Se (HCl): Dried POSS-Se (HCl) (2.5 mg) was added into deionized water (25 mL) and the resulting suspension (0.1 mg/mL) was dispersed with an ultrasonic dispersion instrument. To explore the sensing properties of POSS-Se (HCl) towards Hg2+, the fluorescence spectra of the resulting suspensions were recorded by the fluorescence analyzer upon the addition of successive concentrations of HgCl2 (0–100 ppm) in aqueous solutions.The typical procedure for the detection of Hg2+: The fluorescence emission spectra of POSS-Se (HCl) suspension (0.1 mg/mL) were first measured upon the addition of 100 ppm of metal ions with various cations, including Zn2+, Cr3+, Ca2+, Mn2+, Pb2+, and Cu2+. Then the competitive experiment was conducted by recording the fluorescent spectra of the POSS-Se (HCl) suspensions (0.1 mg/mL) in the coexistence of equivalent Hg2+ and other interfering metal ions (100 ppm).Selective detection of Hg2+ ions. The LOD was calculated using the following Equation (1).The limit of detection (LOD) was calculated based on the fluorescence titration. The standard deviation of a blank measurement was achieved by measuring the fluorescence emission spectrum of POSS-Se (HCl) suspension in water 6 times. To obtain the slope, the ratio of emission intensity at 385 nm was plotted as a concentration of Hg2+ ions.σ = Standard deviation of blank measurement; K = Slope between the ratio of emission intensity versus the concentration of Hg2+ ions were conducted by POSS-Se suspension in water (1 mg mL−1) at room temperature. After the adsorption, the residual concentration of Hg2+ ions was measured by the atomic absorption spectrophotometer or ICP-MS. All the adsorption experiments of Hg2+ concentration was investigated at a series of concentrations including 100, 200, 500, 700, 1000, 2000, 3000, 4000, and 5000 ppm for 24 h equilibrium time in the presence of POSS-Se (1 mg mL−1).The effect of initial Hg2+ ions (1000 ppm) and POSS-Se (1 mg mL−1) and the concentration of Hg2+ ions were stirred at 1, 2, 3, 4, 5, 12, 24, 36, and 48 h.The effect of contact time was investigated by an aqueous solution of Hg2+ ions was estimated by using POSS-Se (1 mg mL−1) to remove Hg2+ ions with a concentration in the range of 50–5000 ppm in aqueous solutions. The effect of the co-existence of various metal ions, including Zn2+, Cr3+, Ca2+, Mn2+, Pb2+, and Cu2+ on the removal efficiency of Hg2+ was further measured by using POSS-Se (1 mg mL−1) to remove Hg2+ ions (100 ppm) in the presence of the competitive metal ions with a concentration of 100 ppm in aqueous solutions.The removal efficiency of HgLK (L mg–1) and mQ (mg g−1) represent the Langmuir constant and the maximum adsorption capacity as calculated by the Langmuir model.The adsorption equilibrium isotherm and relevant parameters were used to determine the adsorption mechanism and modeled using the Langmuir models (Equation (2)).eQ and tQ (mg g−1) are the saturated uptake and the uptake at time t (h), respectively; k2 is the adsorption rate constant of the pseudo-second-order-model.The adsorption kinetics was explored using the pseudo-second-order adsorption models. The linear forms of these models are expressed according to Equation (3).2+ ions was evaluated by considering the desorption and re-adsorption capability. The first adsorption experiment was performed with 5 mL of suspension in water containing Hg2+ ions (1000 ppm) and POSS-Se (1 mg mL−1) for 3 h. Then the suspension was centrifuged. After removing the supernatant, 5 mL of deionized water was added. The resultant suspension was dispersed with ultrasonic dispersion instrument and centrifuged again. The washing and centrifugation process were repeated three times, affording the adsorbed product, POSS-Se+ Hg2+. Then the desorption experiment was performed by adding 12 mL of sodium diethyldithiocarbamate (DDTC-Na) in aqueous solution (90 mg mL−1) and 21 mL of CH3CN to the adsorbed product and subsequently dispersing under ultrasound for 30 min. After centrifuging the resulting suspension and removing the supernatant, the obtained POSS-Se was washed with 12 mL of water and 21 mL of CH3CN to remove residual desorbents. Then the recycled POSS-Se was utilized for the next adsorption experiment. The recycling experiments were performed 10 times.The recyclability of POSS-Se towards Hg2CO3 at room temperature, affording the final product POSS-Se as a white solid in a high yield. In addition, a model compound (MC) was also prepared using a similar method from 4-vinylbenzyl chloride, 1-methylimidazole, and selenium powder [N,N’-dimethyl formamide, but insoluble in methanol, diethyl ether, acetone, and water. This difference is obviously due to the presence of the inorganic–organic Si–O–Si cage and the bulky structure of POSS-Se.As illustrated in m powder   in M-2 and disappears in POSS-Se, indicating the successful reaction between M-2 and selenium powder. In the 13C NMR spectra (CH–N–), while the formed selenone carbons gives rise to a peak at 156.6 ppm. The 29Si NMR spectra reveal one signal at −73.1 and −79.5 ppm for M-2 and POSS-Se  of ca. 295 °C, which was evaluated by thermal gravimetric analysis (TGA) under N2 in the range of room temperature to 600 °C with a heating rate of 10 °C min−1  into POSS-Se suspension in water (0.1 mg mL−1) (2+ by observing a vivid color change [−1. Upon the addition of Hg2+ ions (100 ppm), the suspension showed an obvious color change from dark yellow to pale yellow within 30 s (2+ by POSS-Se (HCl). In addition, upon the completion of the detection, the formed complex can be easily obtained by filtering the suspension, indicating its potential as a candidate for the removal of Hg2+ from aqueous solutions (see the next part).Fortunately, POSS-Se can be well-dispersed in water, which is beneficial for the detection. It was found that there is no color change upon the addition of Hgr change ,36. Motiλmax) at 385 nm. Upon the addition of Hg2+, no obvious change of emission intensity and only a small red-shift of ca. 20 nm were observed. This finding could explain why POSS-Se is not sensitive for the detection of Hg2+. In contrast, the acid treatment of POSS-Se leads to a large fluorescence quenching, indicating that POSS-Se has successfully reacted with HCl and thus a vivid color change occurred. Interestingly, the fluorescence quenching is recovered after adding Hg2+ and the resulting emission spectrum is nearly the same as that of POSS-Se + Hg2+. This finding means that Hg2+ ions have reacted with the acid product POSS-Se (HCl) and afford the same product, which was formed by the direct reaction of POSS-Se and Hg2+.To obtain a deep understanding of the detection process, the fluorescent emission spectra of POSS-Se suspensions before and after the detection were measured. As shown in 2, resulting in the formation of Hg–Se coordination bonds accompanied by the destruction of Se–Se bonds. Thus the color turns pale yellow. In one word, the detection of Hg2+ by POSS-Se is due to the Se–Se formation by acid-treatment and subsequent coordination-induced cleavage of Se–Se bonds upon the addition of Hg2+. From the viewpoint of fluorescence variation, the fluorescence quenching after the acid treatment of POSS-Se can be explained by the formed ionic units, which may act as a fluorescence quencher. After adding Hg2+, the ionic units were converted to the initial state, i.e., selenone, while the Hg–Se coordination bonds were formed. Subsequently, the fluorescence intensity was recovered.The detection mechanism was previously demonstrated in imidazoline-2-selone  and anal2+ to POSS-Se (HCl) suspension in water. The colors of the suspensions gradually turned from dark yellow to pale yellow with increasing concentrations of Hg2+  and the concentrations of Hg2+ ions. POSS-Se (HCl) exhibits a high sensitivity towards Hg2+ with a low LOD of 8.48 ppb pyridine, 1.40 ppm) [2-MIL-53(Al), 30.13 ppb (0.15 μM)) [2@PBATPA, 37 ppb) [To further investigate the detection behavior, the detection was performed by adding successive concentrations from 0 to 100 ppm of Hg of Hg2+ a, while  of Hg2+ b. This f8.48 ppb c. The ac.40 ppm) , metal-o.15 μM)) , nature .15 μM)) , silica  37 ppb) , and ves 37 ppb) , but low 37 ppb) , and sul 37 ppb)   towards common metal ions such as Zn2+, Cr3+, Ca2+, Mn2+, Pb2+ and Cu2+ were first performed in water with a concentration of 100 ppm. As shown in 2+ (100 ppm) mixed with various metal ions . It was found that the fluorescence enhancement changes are negligible after adding other metal ions  using POSS-Se and the acid product POSS-Se (HCl) as the adsorbents as suspension in water (1 mg mL−1). POSS-Se and POSS-Se (HCl) were determined to be 639 and 539 mg g−1, respectively. The lower capacity after the acid treatment is due to the increased molecular weight, while the capacity is calculated in terms of “mg g−1”. This finding reveals that for the adsorption of Hg2+, the acid treatment of POSS-Se is not necessary. Thus we used POSS-Se as the adsorbent to investigate the adsorption behavior towards Hg2+. Developing an efficient adsorbent for simultaneous detection and removal of Hg POSS-Se b. Howeve2+, equilibrium values were collected by adding Hg2+ aqueous solutions with the initial concentrations from 50–5000 ppm. As shown in 2+ concentrations, which can be explained by the driving force of the concentration gradient. The equilibrium adsorption isotherm data was well-fitted with the Langmuir model, yielding a correlation coefficient of 0.9941 (−1 of Hg2+ (the capacity of POSS-Se (HCl) is 907 mg g−1, which was determined under the same method to that of POSS-Se). This value is higher than most reported Hg2+ adsorbents, such as NH2-MIL-53(Al) (153.85 mg g−1) [−1) [−1) [2-G0-SA∼SiO2-G2.0-SA (363.07 mg g−1) [−1) [To evaluate the overall capacity of POSS-Se for Hgf 0.9941 b. Moreov mg g−1) , MA−SAPQ−1) [−1) , sulfur-−1) [−1) , SiO2-G0 mg g−1) , and TAP2+ concentration of 1000 ppm. It can be observed that the initial Hg2+ adsorption rate was rapid during the early stage of the adsorption within 3 h, and the capacity reached 608 mg g−1. After that, the adsorption rate gradually slowed down, leading to equilibration at ~24 h, while the capacity reached 640 mg g−1. The initial high rate may be caused by the higher Hg2+ concentration gradient and ready accessibility of Hg2+ to the binding sites. It could be speculated that the dispersibility of POSS-Se in water would become worse with an increment of the adsorption amount of Hg2+. Moreover, the adsorption kinetic process was well fitted with the pseudo-second-order kinetic model, yielding a correlation coefficient of 0.9999  to remove Hg2+ ions with a concentration in the range of 50–5000 ppm. As expected, on increasing the concentration of Hg2+, the removal efficiency gradually decreases (2+ level at 50 and 10 ppm can be reduced to 3 ppb and 0.5 ppb (well below the permissible level (2 ppb) for drinkable water) with the efficiency of 99.994% and 99.995% within 12 h. In addition, the effect of the co-existence of various metal ions, including Zn2+, Cr3+, Ca2+, Mn2+, Pb2+, and Cu2+ on the removal efficiency of Hg2+ was also studied. It was found that the presence of other metal ions barely affected the removal efficiency of Hg2+ by POSS-Se (In addition to the high Hgecreases a. Howeve POSS-Se b.2+ ions. By using sodium diethyldithiocarbamate (DDTC-Na) as the chelating reagent [2+ ions can be easily removed from POSS-Se within 30 min. Thus, the adsorption–desorption process was repeated 10 times by using 5 mL of suspension in water containing Hg2+ ions (1000 ppm) and POSS-Se (1 mg mL−1) for 30 min as the standard experiment. The relative adsorption capacity was calculated on the basis of the adsorption capacity determined in the first cycle as a benchmark before and after adsorption. In the first cycle, the adsorption capacity was regarded as 100%. After desorbing the Hg2+ ions by DDTC-Na, the recovery of the relative adsorption capacity was 94%. After ten cycles, the capacity recovery was 70.5% , which is comparable to many reported Hg2+ sensors. Moreover, POSS-Se possesses a high adsorption capacity (952 mg g−1) for Hg2+ ions in aqueous solutions without the requirement of acid treatment. The performance is better than most reported adsorbents for Hg2+. These results reveal that this novel selenone-functionalized POSS can be potentially utilized as a promising candidate for the detection and removal of Hg2+ from aqueous solutions. Further investigation will focus on the synthesis of novel selenium-containing POSS-based materials and exploration of their applications.In summary, a novel selenone-functionalized polyhedral oligomeric silsesquioxane (POSS-Se) was prepared by the reaction of an imidazolium-containing POSS with selenium powder. After an acid treatment of POSS-Se, the product POSS-Se (HCl) suspension in water can serve as an efficient sensor for the detection of Hg


The use of polyhedral oligomeric silsesquioxanes (POSSs) for making polymer composites has grown exponentially since the last few years of the 20th century. In comparison with the other most commonly used fillers, POSSs possess the advantage of being molecules. Thus, this allows us to combine their nano-sized cage structures, which have dimensions that are similar to those of most polymer segments and produce a particular and exclusive chemical composition. These characteristics linked with their hybrid (inorganic–organic) nature allow researchers to modify POSS according to particular needs or original ideas, before incorporating them into polymers. In this present study, we first start with a brief introduction about the reasons for the rediscovery of these nanoparticles over the last 25 years. Starting from the form of POSS that is most widely used in literature (octaisobutyl POSS), this present study aims to evaluate how the reduction of symmetry through the introduction of organic groups favors their dispersion in polystyrene matrix without compromising their solubility. Undoubtedly, the materials that have characterized the last century, were the polymers, due to their ability to provide economic and structural benefits. Continuing in this direction and trying to improve mechanical, thermal and durability properties of polymers by adding various reinforcements to them, material experts are defining the composites as reference materials for the twenty-first century. In the design and assembly of a composite we have to fish in the sea of chemistry, that as we know contains organic and inorganic materials, each with different characteristic properties. Hence, the idea in developing hybrid compounds involves taking advantage of the best properties of each component and trying to decrease or eliminate their drawbacks. Based on this original idea, the prediction is that the defining material platform of the twenty-first century could very well be the hybrid, where two or more components are combined in a single material to give new and previously unattainable combinations of useful properties . In thisUnlike the other building blocks, for which few traces are found in the literature before the 1980s, the earliest reports of chemistry relating to silsesquioxanes occurred at the end of the nineteenth century, which were produced by Buff and Wohler  and LadeIt increased from an annual average of twenty manuscripts during the five-year period of 1995–2000 to currently reach an annual average of about four hundred manuscripts, with an increase of 2800% starting from 1990 and an increase of 1200% starting from 2000. It is worth noting that in the same period, there has been an overall increase in scientific publications but if we conduct the same operation by entering two other very common search terms, such as Clay or Natural fibers, it can be observed that these terms do not generate a number of manuscripts that is half the number of publications related to the POSS term.Air Force Research Laboratory at the Edwards Air Force Base , where he studied POSS-containing polymers as precursors to hybrid inorganic/organic materials. He subsequently founded the Hybrid Plastics company in 1998, which is actually recognized as the commercial leader for POSSs production. Thus, the most common POSSs are manufactured on a large scale nowadays so that researchers worldwide may purchase these nanomaterials at very competitive prices. Furthermore, the organic nature of the POSSs periphery, which we will analyze in detail later in the text, can be functionalized to generate hundreds of possible compounds. Both purchased and modified POSSs are extremely versatile and may be chemically bonded or physically blended into a companion material, resulting in a hybrid nanomaterial with the combined benefits of POSS and the companion material [The rediscovery of these materials is certainly due to the work of Feher who set up their synthesis with easily reproducible methodologies ,22 and L1.5)n, where R is H or an organic group , are also known as Polyhedral Oligomeric Silsesquioxanes. These chemicals are composed of a silicon and oxygen cage, which is externally completed by organic groups that are covalently bonded with the silicon atoms. The most common value of n is 8, thus generating a very highly symmetric structure. This is sometimes indicated in the literature with the symbol T8, which has a diameter that is usually in the range of 1.5–3 nm 4 [The various POSSs were prepared by a corner capping reaction of trisilanol with aryltrimethoxysilane or phenyltrimethoxysilane. Isobutyltrimethoxysilane, cyclopenthyltrimethoxysilane and phenyltrimethoxysilane were purchased from Aldrich Co. . and used as received. Trimethoxysilane derivatives were prepared from the appropriate Grignard reagent and Si(OCH3)4 ,27,28,293)4 . The varPOSSs have shown interesting thermal, mechanical, optical and electrical properties ,32,33,34Tg), suggesting a preference in self-regulating phenomena for the symmetric POSS as opposed to the asymmetric ones , which aimed to obtain nanocomposites with more thermal stability than the matrix. The corner capping reaction of trisilanol with trichlorosilane and/or triethoxysilane ,46 was cric ones . A good Finally, SEM analyses showed the presence of aggregated POSS when oib-POSS is used to reinforce PS, which resulted in a better dispersion of nanoparticles when ph, hib-POSS was used ,51.T5%  and Ea of degradation  values in an oxidative environment. The increasing trend albeit slightly less dramatic was also observed for the degradations performed in an inert atmosphere for both T5%  and Ea of degradation (+49 kJ/mol with respect to PS). The greater reinforcement, which was due to the replacement of isobutyl with phenyl groups in the POSS corona, was confirmed by the calorimetric experiments carried out to measure the glass transition temperature of the prepared nanocomposites with polystyrene. We observed a Tg value that was increased by 28 °C compared to that of the oib-POSS/PS nanocomposite and increased by 12 °C compared to that of the ph, hib-POSS/PS nanocomposite. Thus, this supports the hypothesis that the synergistic effect from the introduction of more rigid  phenyl groups with maintenance of the asymmetric structure (by replacing 7/8 organic group at vertices of silicon cage) leads to an increase in the thermal stability of the resultant nanocomposites.The next step of the research was the synthesis of POSSs with seven phenyl and one alkyl group  in order to create the relative PS based nanocomposites . In this case, a thermal investigation was carried out, which showed a dramatic increase in both T5% values of all prepared nanocomposites in both oxidative and inert environments were much higher than those of neat PS and slightly higher than those of ib, hph-POSS/PS nanocomposites . The Tg value remained practically the same as that observed for the ib, hph-POSS/PS but this value was higher than that of PS.At this stage of the study, the only possibility to further improve the reinforcing effect while still keeping these two points  involves obtaining soluble POSSs without a large decrease in the initial decomposition temperature with respect to that of commercial octaphenyl POSS. This can be achieved through the replacement of only one hydrogen atom on one of the eight phenyl groups. Therefore, octaphenyl POSS with small substituents  in the place of one hydrogen atom on one of the eight phenyl groups was synthesized  and usedIn recent years, a particular group of POSSs, which are namely “dumbbell-shaped” POSSs formed by an organic group covalently attached to more than one silicon cage, have attracted particular interest. The change in organic bridge leads to a change in geometry, length, rigidity and functionality of obtained POSS, which allows us to subsequently tune its bulk properties ,53,54. PT8 cage into PS. For this reason, we synthesized dumbbell-shaped POSSs with a simple and functionalized aromatic bridge using the well consolidated corner capping reaction  [T5% values of about 290 °C in nitrogen and 260 °C in air) [Once synthesized and thermally characterized, a comparison was made with the unbridged systems, dumbbell shaped POSS showed a better thermal stability (yl POSS) ,59. Whenyl POSS)  which waIn order to improve the dispersion of these new very thermally stable nanoreinforcements in the polystyrene matrix, the next design step was to synthesize a series of dumbbell-shaped POSSs with an aliphatic bridge instead of the aromatic one . The resIn terms of the chemico-physical behavior, we found an increase in the resistance to the thermal degradation with respect to the PS reinforced with the POSS bearing an aromatic bridge, which was measured by the initial decomposition temperature and increased as a function of the alkyl bridge length .Concerning the synthesis of differently characterized POSSs and their incorporation into the polystyrene matrix, it is possible to draw a series of conclusions that can be useful for the designing of nanostructured polymers based on polyhedral oligomeric silsesquioxanes.By taking for granted that the phenyl groups confer greater thermal stability to the resulting composites, which is supported by the literature , this prTherefore, in the designing of these materials we must ask whether the priority should be the dispersion in the matrix, and then the possibility to opt for the asymmetric un-bridged POSSs, or a higher compatibility with the polymer and then the possibility to opt for the symmetric, but with a bridge that can be functionalized, dumbbell shaped POSSs. An alternative route was proposed, which involved the addition of an aliphatic bridge, which allows the freedom of movement of silicon cages. Due to the spatial blockage, this cannot be achieved with an aromatic bridge.


Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practice are still not known. To give a comprehensive understanding of Fuzi-induced toxicities, current study is proposed aiming to investigate the biodistribution of the six toxic alkaloids in Fuzi, namely Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), Benzoylaconine (BAC), Benzoylhypaconine (BHA) and Benzoylmesaconine (BMA), after its oral administrations at clinically relevant dosing regimen. A ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for simultaneous quantification of six toxic alkaloids in plasma, urine and major organs of Sprague Dawley rats after oral administrations of two commonly used Fuzi preparations, namely Heishunpian and Paofupian, at their clinically relevant dose for single and 15-days. Among the studied toxic alkaloids and organs, BMA demonstrated the highest concentrations in all studied organs with liver containing the highest amount of the studied alkaloids, indicating their potential hepatotoxicity. Moreover, tissue accumulation of toxic alkaloids after multiple dose was observed, suggesting the needs for dose adjustment and more attention to the toxicities induced by chronic use of Fuzi in patients.Although  Radix Aconiti Lateralis is known as Fuzi, an extensively used traditional Chinese medicine in China and other Asian countries [The processed lateral root of ountries . Fuzi isountries ,2. Amongountries . In clinountries .Although Fuzi has promising therapeutic effects, aconitum poisoning has been extensively reported with 17 cases from Taiwan during 1990–99, 39 cases form Hong Kong during 2012–19, 2017 cases from mainland of China during 1989–2008, and 121 cases from Korea during 1995–2007 ,5. In cl19-diterpenoid alkaloids, including three di-ester diterpenoid alkaloids (DDAs) and three mono-ester diterpenoid alkaloids (MDAs) [8 and become MDAs. Based on their LD50 values on mice, the toxicities of MDAs were 1/700–1/100 of that of DDAs [14 to generate non-toxic non-ester type alkaloids (NDAs) [The principal toxic ingredients in Fuzi are Cs (MDAs) . As shows (NDAs) .+-Ca2+ exchange system [2+-ATPase [Previous mechanistic studies on Fuzi-induced toxicity mainly focused on the cardiotoxicity of the DDAs. The DDA-induced arrhythmogenic effects, which have been frequently observed after ingestion of Fuzi, were well recognized to be caused by activating the voltage-dependent sodium channel on the cell membranes in excitable tissues such as myocardium ,12,13,14+-ATPase . In addi+-ATPase , brain [+-ATPase , and kid+-ATPase .Based on various processing methods used by Chinese medicine practitioners, there are ten types of Fuzi preparations ,20,21, aThe concentrations of the toxic alkaloids DDAs in plasma and cardiac tissue have been found positively correlated with the cardiac toxicity after single dose of Fuzi in mice and rats , suggestTo give a more complete understanding of the biodistribution profiles of toxic alkaloids to see how they relate to Fuzi-induced toxicities, the current study was conducted to establish an LC/MS/MS method for simultaneous determination of six toxic aconitum alkaloids in rat plasma, urine and major organs, followed by its application to investigate their biodistributions after single and 15-day oral administrations of Heishunpian and Paofupian at their clinical dosing regimen in rats.The optimal parameters including precursor ion, product ion, fragmentor and collision energy are listed in Solid phase extraction (SPE) using a mixed-mode cation-exchange (MCX) cartridge was adopted to separate the targeted toxic alkaloids from the biological matrix in brain and liver homogenates. According to previous published studies , 5% ammo2 ≥ 0.99) in plasma (0.5–100 ng/mL), urine (0.5–200 ng/mL) and different organs (range from 0.5 to 200 ng/mL). Lower Limit of Quantification (LLOQs) in plasma was 0.5 ng/mL, while no higher than 2 ng/mL in urine and different organs. The results for intra- and inter-day accuracy and precision are shown in As demonstrated in The stability results were also shown in Contents of the six toxic alkaloids in Heishunpian and Paofupian are depicted in Based on the contents of six toxic alkaloids in two Fuzi preparations, the toxic alkaloid dosages of 30 g/kg Heishunpian in rat were: BMA (1814 μg/kg), BHA (321 μg/kg), BAC (254 μg/kg), HA (6.61 μg/kg), AC (0.39 μg/kg) and MA (0.38 μg/kg), and the toxic alkaloid dosages of 30 g/kg Paofupian were: BMA (1430 μg/kg), BAC (227 μg/kg), BHA (150 μg/kg), HA (0.07 μg/kg), MA (0.05 μg/kg) with no detectable AC.Toxic alkaloid concentrations in rat tissues after oral administrations of 30 g/kg Heishunpian and 30 g/kg Paofupian both for single dose and multiple dose to rats are illustrated respectively in Consistent with their contents in the dosed Fuzi preparations , the conAmong all the studied organs, liver contained highest amount of all detectable toxic alkaloids. Closely following liver, kidney contained relative high concentration of toxic alkaloids. Only once exception occurred in biodistribution of BHA after multiple dose of Paofupian, where concentration of BHA in kidney went beyond that in liver.In addition to plasma and organs, concentration of toxic alkaloids in urine had also been tested. Althought no difference was shown after single or multiple dose of Paofupian, after oral administration of Heishunpian, more numbers of studied toxic alkaloids could be detected in urine sample  than that in plasma sample . Furthermore, concentrations of toxic alkaloids in urine were 10–80 times higher than those in plasma after dosing Heishunpian or Paofupian to rats.Tissue accumulation of MDAs due to long-term treatment–giving Heishunpian or Paofupian preparation once daily for consecutive 15 days–was clearly observed a,b. CompSince the doses of each toxic alkaloids in two Fuzi preparations varied, the contents of toxic alkaloids in each organ were normalized by their individual doses as shown in Dose-normalized toxic alkaloid contents in each organ were adopted for comparison of the biodistribution of toxic alkaloids between two different Fuzi preparations, Heishunpian and Paofupian. It could be summarized from Existing studies mainly focused on cardiac toxicities induced by DDAs from Fuzi. Mechanisms behind DDAs-induced arrhythmogenic effects have been well elaborated ,13,14,15−5%, and 4.11 × 10−7% respectively. The DDA contents in both two preparations were much less than 0.01%—the criteria listed in 2015 Chinese Pharmacopoeia [Different contents of six alkaloids in the two studied Fuzi preparations were highly related to different processing procedure of Heishunpian and Paofupian. Paofupian had one more step of roasting with sands to do from Heishunpian. Long time high temperature condition facilitated the hydrolyzation of DDAs and MDAs to MDAs and NDAs . As a reacopoeia . TherefoOur biodistribution data for the first time revealed the effect of long-term dose of Fuzi preparations (both Heishunpian and Paofupian) on the biodistribution profiles of toxic alkaloids. It was found that long-term exposure of Fuzi preparation could lead to significant accumulation of MDAs in liver, kidney and heart, while no accumulation was found for DDAs. Since the phase I and phase II metabolic rate of MDAs in human liver microsome are less than 10% , the acc50 for a single oral dose of MDAs in mice , MDAs wIn addition, our findings also revealed that the biodistributions of six toxic alkaloids from the two Fuzi preparations still differed from each other even after dose normalization, . Such di50 values [It was also noted that the dose-normalized contents of DDAs were higher than those of MDAs in majority of studied organs . One of 0 values . TherefoOur findings on higher possibility of toxic alkaloids occurrence in urine sample when compared to plasma sample provided a reasonable explanation of a previous clinical poisoning case  reportedLast but not the least, current findings confirmed that the toxic alkaloid levels were remarkably high in the liver and kidney, relatively low in the heart and blood with only a trace amount recovered in the cerebrum, consistent with previous biodistribution result in clinical poisoning cases  and precThe current developed and optimized LC/MS/MS method for quantitative determination of the six toxic aconitum alkaloids was specific and sensitive for biodistribution study in rats. Among the six toxic alkaloids, BMA had the highest content in the investigated Fuzi preparation, which also led to its highest content in rat tissues.Our current study for the first time demonstrated not only the remarkably high tendency of toxic aconitum alkaloids distributing into the liver and kidney, but also their significant accumulation in major organs after long-term oral administrations of the Heishunpian and Paofupian concentrated granules at clinically relevant dosage to rats. Therefore, clinical use of Fuzi in patients with sub-chronic and even chronic disease may need more precise adjustment on dosage and more attention to liver injury induced by Fuzi. Additionally, our study revealed that co-occurring components existing in Heishunpian increase the in vivo exposure and tissue content of six toxic aconitum alkaloids existing in Fuzi.All the reagents used in the current study were at least of analytical grade. Formic acid was supplied by BDH Laboratory Supplied Ltd. . Acetonitrile and methanol were purchased from RCI Laboscan Ltd.  and both of them were HPLC-grade. Deionized water was used for the preparation of all solutions. Six toxic aconitum alkaloids, including aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine and benzoylmesaconine, and Berberine hydrochloride which was used as internal standard (IS) were all purchased from Sigma-Aldrich . Heishunpian or Paofupian concentrated granule were obtained from Purapharm Co., Ltd. .Adult male Sprague Dawley rats (weighing 200–220 g) were supplied by the Laboratory Animal Services Centre, the Chinese University of Hong Kong, HKSAR, China. This study was approved on 9 February 2018 by the Animal Experimentation Ethics Committee of the university (Reference No. 17/219/HMF-5-B).Separation and quantification of DDAs including Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), MDAs including Benzoylaconine (BAC), Benzoylhypaconine (BHA), Benzoylmesaconine (BMA) and internal standard (Berberine) were performed on Agilent 1290 Ultrahigh performance liquid chromatograph coupled to an Agilent 6430 Triple Quad LC/MS (UPLC–MS/MS) with electrospray ionization (ESI) . A Waters Acquity UPLC BEH C18 column  was used for chromatographic separation. The mobile phase was composed of an aqueous solution of 0.1% formic acid (Solvent A) and acetonitrile containing 0.1% formic acid (Solvent B). The gradient profile was as follows: 0–4 min with a linear gradient of B from 10 to 45 % and 4–8 min with a linear gradient of B from 45 to 70%, for 8–9 min the composition of B is maintained at 70%, finally the column was re-equilibrated. The flow rate was 0.15 mL/min. The injection volume was 10 μL. The entire eluent was ionized via an ESI source operating in the positive mode and monitored by MS/MS detection in the multiple reaction monitoring (MRM) mode. The optimization of the MS/MS conditions were conducted by directly injecting the individual analyte solutions in methanol at a concentration of 500 ng/ml with a mobile phase composition and flow rate equivalent to those at the time the analyte would elute from the UPLC column.v/v, containing 2.5% formic acid) to obtain a stock solution (1 mg/mL). The stock solutions of each tested alkaloid were then mixed accordingly to obtain a stock solution containing 1 mg/mL of each toxic alkaloid. Tested alkaloid (1 mg) was dissolved in 1 mL 50% methanol in water  samples in granule content determination) or deionized water (for QC samples in rat tissue content detection to a series of concentration level ranging from 0.5–1000 ng/mL). Detailed concentration levels depended on sample content in various matrix to be tested as shown in The stock solutions with mixed alkaloids were diluted with 50 % methanol in water . After washing the cartridge with 1 mL of 0.1 M HCl in H2O followed by 1 mL of methanol, the analytes were eluted with 750 μL methanol containing 5% ammonium hydroxide.For liver and brain sample preparations, 300 μL of their homogenate was loaded to MCX cartridge  , includiThe specificity of the method was conducted by comparing the chromatographs of blank rat plasma, urine and organ homogenate samples with that of blank rat samples spiked with standard solutions and rat plasma/brain homogenate after oral administration of Heishunpian or Paofupian.2) was calculated, which with a value greater than 0.99 was considered as an indicator of good linearity. The lower limit of quantification (LLOQ) was defined as the lowest concentration of the calibration curve with a signal-to-noise (S/N) peak ratio greater than 5:1.Calibration samples were prepared as described in The intra-day accuracy and precision test were conducted by analyzing QC samples at nominal concentrations . Recoveries and matrix effects of six toxic alkaloids at the levels of Limit of Quantification (LOQs), Middle of Quantification (MOQs) and High of Quantification (HOQs) should be consistent and reproducible.The recovery of extraction was determined by the peak area of six toxic alkaloids spiked with the biological matrices followed by extraction against the peak area of six toxic alkaloids spiked to the extracted biological matrices. The matrix effects caused by different biological matrix including plasma, urine, liver, kidney, brain and heart homogenate were calculated by comparing the standard curve in above biomatrix with that in 50% methanol in water  was mixed with 200 μL 20 ng/mL internal standard then injected into LC/MS/MS spectrometry, focusing on DDAs quantification. The other filtrate need be 20 times diluted before mixing with internal standard, focusing on MDAs detection. The content of DDAs come from per gram Fuzi processed herb will be indicated as DDAs percentage (%) and calculated by following Equations (1–2) for its comparison with those criteria for Fuzi processed product:n = 8 for each group) at a bolus of 6 g/kg  for both one time and once daily lasting 15 days.Commercially available concentrated granules of Heishunpian and Paofupian were orally given to Sprague Dawley rats  were suspended in 10 mL boiling water followed by sonication until evenly suspense in water. Since reported cardiotoxicity usually happened at 1–2 h post-dosing [Toxic alkaloid contents were expressed as the mean ± standard deviation. To give further explanation to biodistribution results, dose-normalized content of toxic alkaloid in each organ is calculated using following Equations (3)–(5). For Paofupian treated group, the dose on last day was served as dosed alkaloid content to calculate dose-normalized content of toxic alkaloid in each tissue.Partition coefficient parameter (LogP) of studied six toxic alkaloids from Fuzi was calculated using ALOGPS 2.1 software.


The sphingolipid (SL) metabolic pathway generates structurally diverse lipids that have roles as membrane constituents and as bioactive signaling molecules. The influence of the SL metabolic pathway in biology is pervasive; it exists in all mammalian cells and has roles in many cellular and physiological pathways. Human genetic diseases have long been recognized to be caused by mutations in the pathway, but until recently these mutational defects were only known to affect lysosomal SL degradation. Now, with a nearly complete delineation of the genes constituting the SL metabolic pathway, a growing number of additional genetic disorders caused by mutations in genes within other sectors of the pathway  have been recognized. Although these inborn disorders of SL metabolism are clinically heterogeneous, some common pathogenic mechanisms, derived from the unique properties and functions of the SLs, underlie several of the diseases. These mechanisms include overaccumulation of toxic or bioactive lipids and the disruption of specific critical cellular and physiological processes. Many of these diseases also have commonalities in physiological systems affected, such as the nervous system and skin. While inborn disorders of SL metabolism are rare, gene variants in the pathway have been linked to increased susceptibility to Parkinson’s disease and childhood asthma, implying that the SL metabolic pathway may have a role in these disorders. A more complete understanding of the inborn errors of SL metabolism promises new insights into the convergence of their pathogenesis with those of common human diseases.  The metabolic pathway for sphingolipids (SLs), in various iterations, is a feature of all mammalian cell types . Its mosMutational defects in the SL metabolic pathway, notably in lysosomal degradation, cause some of the oldest human metabolic diseases described. In recent years, the nearly complete inventory of the genes controlling the SL metabolic pathway, along with the advent of whole-exome sequencing analysis, has allowed the recognition, perhaps not surprisingly, of a growing number of additional disorders arising from genetic defects throughout the pathway  and ceramide produce a number of distinct human diseases . For exaeoxy-SLs , 11. DesKDSR cause inherited disorders of keratinization associated with thrombocytopenia , which catalyzes the formation of C18 ceramides and is highly expressed in the brain, causes a novel progressive myoclonic epilepsy associated with neurodegeneration  deficiency, which was originally identified in Old Order Amish individuals, is responsible for an autosomal recessive infantile-onset symptomatic epilepsy syndrome associated with intractable seizures, developmental stagnation, extreme irritability, failure to thrive, cortical blindness, and cutaneous dyspigmentation (B4GALNT1) has been described in individuals with a complex form of hereditary spastic paraplegia  yields the nonSL substrates hexadecenal and phosphoethanolamine. For transfer to the glycerophospholipid pathway, hexadecenal is oxidized to hexadecenoic acid by the fatty aldehyde dehydrogenase encoded by the ALDH3A2 gene. After CoA addition, hexadecenoyl-CoA is saturated to palmitoyl-CoA . Ac. AcACER3 defects . While tSGPL1 gene cause a recently recognized syndrome of steroid-resistant nephrotic pathologies associated with facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects called nephrotic syndrome type 14 , a very severe disorder associated with ichthyosis , metachromatic leukodystrophy , and Gaucher disease  . These fhthyosis  41)..GBA1), aGBA1) carrier status as the most common risk factor for Parkinson’s disease (PD) and Lewy body dementia . Impaired autophagy, a result of SL storage, has been implicated in the pathogenesis of SL LSDs, including Sandhoff and Gaucher diseases  42–44).–44.42–44dementia . Lysosomand GALC  47, 48), 48GBA1)The inborn errors of SL metabolism now comprise disorders caused by mutations in more than 20 different genes in the SL pathway . AlthougGBA1 and ORMDL3, respectively, tying these disorders directly to the SL metabolic pathway (Although the inborn errors of SL metabolism are rare diseases, a detailed understanding of their pathogenic mechanisms can illuminate our understanding of common diseases. Susceptibility to PD and childhood asthma have been linked to genetic variants of  pathway , 45, 46. pathway , 50.The significant advances made in our understanding of the biochemistry and genetics of the SL metabolic pathway have enabled the identification of new human genetic disorders beyond those in lysosomal SL degradation. This more complete understanding of the entire group of inborn errors of SL metabolism is yielding novel insights into disease mechanisms that are relevant to the pathogenesis of common human diseases.


Epilepsy surgery is a clinical procedure that aims to remove the brain tissue responsible for the emergence of seizures, the epileptogenic zone (EZ). It is preceded by an evaluation to determine the brain tissue that must be resected. The identification of the seizure onset zone (SOZ) from intracranial EEG recordings stands as one of the key proxies for the EZ. In this study we used computational models of epilepsy to assess to what extent the SOZ may or may not represent the EZ. We considered a set of different synthetic networks  to represent large-scale brain networks and a phenomenological network model of seizure generation. In the model, the SOZ was inferred from the seizure likelihood (SL), a measure of the propensity of single nodes to produce epileptiform dynamics, whilst a surgery corresponded to the removal of nodes and connections from the network. We used the concept of node ictogenicity (NI) to quantify the effectiveness of each node removal on reducing the network's propensity to generate seizures. This framework enabled us to systematically compare the SOZ and the seizure control achieved by each considered surgery. Specifically, we compared the distributions of SL and NI across different networks. We found that SL and NI were concordant when all nodes were similarly ictogenic, whereas when there was a small fraction of nodes with high NI, the SL was not specific at identifying these nodes. We further considered networks with heterogeneous node excitabilities, i.e., nodes with different susceptibilities of being engaged in seizure activity, to understand how such heterogeneity may affect the relationship between SL and NI. We found that while SL and NI are concordant when there is a small fraction of hyper-excitable nodes in a network that is otherwise homogeneous, they do diverge if the network is heterogeneous, such as in scale-free networks. We observe that SL is highly dependent on node excitabilities, whilst the effect of surgical resections as revealed by NI is mostly determined by network structure. Together our results suggest that the SOZ is not always a good marker of the EZ. Depending on Ii (t), the node is either at a fixed stable phase Ii < 0), or oscillating in a limit cycle (Ii > 0). The boundary Ii = 0 between the two states corresponds to a saddle-node on invariant circle (SNIC) bifurcation. This simple model has been shown to be a computationally efficient and a reliable approximation of a more complex and biophysical realistic model of epileptiform dynamics  are noisy inputs, K is the global scaling coupling of network interaction, aji is j,ith entry of the adjacency matrix that encodes the network, j, and 2. Each node receives independent noise,where i)((t) = 0 and K = 0),The steady state s). For a fixed global coupling K, SLi)  ( = 0). In this framework the EZ corresponds to the nodes with highest NI. Whereas, SL is based solely on a presurgical network, using SOZ as a proxy for the EZ, NI quantifies the result of different possible surgical resections by comparing the dynamics of a post-surgical network with the presurgical network, therefore using in silico surgeries to define the EZ.where SL is equivalent to NI to clarify whether the SOZ is concordant with the EZ in silico. Assuming that the SOZ is predictive of the pathological tissue that must be resected, then we would expect a high correlation between SL and NI. We use a weighted Kendall's rank correlation measure , and Q is the number of groups in reverse order. We take into account the relative values of SL and NI by weighting each contribution to P and Q by the product of the distances in SL and NI, |SLi)( − SLj)(| × |NIi)( − NIj). The small-world properties of these networks were confirmed using the small-world measure  with higher excitabilities  in networks with homogeneous excitabilities . SL and NI in undirected networks (mean degree c = 8). τ accounts for the relation between orderings, whereas ρ is the Pearson correlation between SL and NI distributions. As observed in SL and NI and consequently yield low correlations between the two distributions . In the case of small-world and random networks, we find a relative agreement between SL and NI distributions (ρ ≈ τ ≈ 0.68), which shows that the two measures are not interchangeable. We also observe that as we consider networks with higher rewiring probabilities p, the concordance between SL and NI increases, which suggests that the relationship between the two measures is enhanced in networks with lower clustering coefficients and lower average path lengths. Furthermore, SL and NI are in conflict with regards to the relative importance of each node to the emergence of seizures. SL and NI.To further characterize the relationship between seizure onset dynamics and underlying ictogenicity, we measured SL and NI distributions become flatter. The decrease in correlation and ordering is most noticeable in small-world and random networks given that these networks are more homogeneous than scale-free networks with respect to node degree. Also, since higher degree exponents α correspond to network more homogeneous, we find that τ and ρ also become small for sufficiently large mean degree and exponent α  we randomly select and attribute high excitability to a group of nodes; and (2) we define excitabilities inversely proportional to node degree.We extend our comparison between SL and NI distributions of regular, small-world, and random networks with randomly located hyper-excitable nodes (SL and NI (τ > 0.99 and ρ > 0.88), with both measures clearly distinguishing the hyper-excitable nodes from the other nodes. These results suggest that the SOZ may be a good predictor of the EZ when brain networks are relatively homogeneous with regards to node degree and focal differences arise from intrinsic tissue heterogeneities. I0 = −1.2). In this case, the agreement between SL and NI is similar to what we have observed in the homogeneous case . These results can be further compared to the case with homogeneous excitabilities , which represent the anatomical structure of the brain's white matter, typically vary in size from 82 to 4,000 nodes (Fornito et al., ML, MG, and JT contributed to the study concept and design, results interpretation, and manuscript drafting and revision. ML performed the computational simulations.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Antibiotics are useful but increasing resistance is a major problem. Our objectives were to assess antibiotic use and microbiology testing in hospitalized children in the Gambia.We conducted a retrospective analysis of paediatric inpatient data at The Edward Francis Small Teaching Hospital in Banjul, The Gambia. We extracted relevant data from the admission folders of all patients (aged > 28 days to 15 years) admitted in 2015 (January–December), who received at least one antibiotic for 24 h. We also reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period.Klebsiella species being the most common , mainly from urine . Antibiotic resistance was mainly to ampicillin , mainly reported as Coliform species 11/51, 21.6%.Over half of the admitted patients received at least one antibiotic during admission (496/917) with a total consumption of 670.7 Days of Antibiotic Therapy/1000 Patient-Days. The clinical diagnoses included an infectious disease for 398/496, 80.2% of the patients on antibiotics, pneumonia being the most common . There were 51 clinically relevant bacterial isolates, More than half of the admitted patients received antibiotics. The reported antibiotic resistance was highest to the most commonly used antibiotics such as ampicillin. Efforts to maximize definitive antibiotic indication such as microbiological testing prior to start of antibiotics should be encouraged where possible for a more rational antibiotic use. Antibiotic resistance is a major problem especially in resource-limited countries where the burden of infectious diseases is high, with often higher resistance rates than in industrialized countries . ChildreStreptococcus species [Salmonella [Helicobacter pylori [. As far as we know there has been no published study examining antibiotic prescribing and microbiological testing patterns in the general paediatric inpatients in the Gambia.Inappropriate antibiotic use is well described in developed countries but not as well studied in developing countries . Local d species , 13, Sallmonella , Helicobr pylori , and forr pylori , within r pylori . But natr pylori . As far Different bacteria use different mechanisms to develop antibiotic resistance as defined by Munita et al. , who claThe study was a retrospective analysis of paediatric inpatient data from The Edward Francis Small Teaching Hospital in Banjul (EFSTH), The Gambia’s largest hospital referral centre. The hospital serves as the country’s main tertiary care centre receiving patients from the whole country. The team of medical doctors responsible for the management of patients include specialists, medical officers, and house officers., antibiotic treatment , and microbiology workup. All the included patients had at least one diagnosis at the time of admission; the diagnoses were mostly clinically based. All the diagnoses included were as documented on the patients’ records. We also obtained information on the total admissions during this period. In addition, we reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period.We extracted the required data from the admission folders of patients aged > 28 days to 15 years admitted in 2015 (January–December), who received at least one antibiotic for at least 24 h, using Microsoft Access 2010. We excluded records of patients discharged against medical advice and admission folders with missing dates or loss of documents containing antibiotic or diagnoses details. Data extracted included: age, weight, height, sex, clinical diagnosisAntibiotic consumption was assessed based on qualitative indicators which assess appropriateness of antibiotic use, and quantitative indicators which assess the volume or cost of antibiotics used . For theFor the quantitative assessment of antibiotic consumption for inpatients, we used the recommended Days of Antibiotic-Therapy (DoT)/1000 Patient-Days (PD) to assess the volume of antibiotics used in the paediatric inpatient setting , since tTo assess the bacteria isolates and resistance test results for the study period, we used the data we obtained from the laboratory records since we assumed that this data may be more complete than those in the admission folders. However, due to lack of the hospital numbers for some of the records, matching of these patients with the admission data was not feasible.We analyzed the data with Stata version 12  using a complete case approach. We summarized the results into proportions, ratios, and medians. Where applicable, we compared children under 5 and those over 5 years of age. To make comparisons and test for associations for antibiotic use, we used Chi square test  and Fisher’s exact test . We set statistical significance at ≤0.05.For the year 2015 (January–December), 917 patients were admitted, 496 (54.1%) received at least one antibiotic and fulfilled the other inclusion criteria for the analysis, 181/496, 36.5% of these also received antibiotics on discharge. The total antibiotic consumption was 670.7 DoT/1000 PD. Most of the patients treated with antibiotics had at least one infectious disease diagnosis (80.2%) , penicillin-G , or ampicillin and gentamicin  as recommended by the WHO: using ampicillin (or penicillin) with gentamicin as first-line or ceftriaxone as second-line for treatment of severe CAP among children aged 2 to 59 months. Other antibiotic combinations used included penicillin-G and chloramphenicol , ceftriaxone and cloxacillin , and ampicillin and cloxacillin . Ampicillin was dosed at 50 mg/kg for eight patients, one patient received a lower dose; penicillin-G was dosed at 50,000 units/kg for 19 patients, two patients received a higher dosage. There was no use of macrolides, tetracyclines or fluoroquinolones.Acinetobacter baumanii, from cerebrospinal fluid, with no reported resistance); ampicillin and gentamicin combination, which were changed to ciprofloxacin ; ampicillin and gentamicin combination, which were changed to ceftriaxone, and later to ciprofloxacin ; ceftriaxone and cloxacillin . Nine (81.8%) of the patients with UTI (11) had cultures requested, of which two (22.2%) had bacteria isolated from urine and were treated with ampicillin and gentamicin combination, later changed to ceftriaxone, with additions of nitrofurantoin and ciprofloxacin during the course of treatment ; ampicillin and gentamicin combination . Thus all the resistant bacteria reported (five) were to ampicillin  and gentamicin . The difference in the choice of antibiotics between these patients with or without positive cultures was not significant.Forty-eight (68.6%) of the patients with sepsis (70) had cultures requested, of which four (8.3%) had bacteria isolated and respectively treated with ceftriaxone and ciprofloxacin , Coliform species  1/11, 9.1%), and S. aureus  1/9, 11.1%) , co-trimoxazole , and gentamicin  3/51, 5.9%, and S. aureus 2/51, 3.9%) .We observed an overall higher antibiotic consumption (670.7 DoT/1000 PD) when compared to that observed from a pre-interventional phase of an ABS study conducted in a paediatric unit in a developed country (483.6 DoT/1000 PD) . The volEmpirical antibiotic indication and dosage for the treatment of severe CAP were as recommended by WHO for most of the patients . A smallAbout half of the patients treated with antibiotics had at least one microbiology test requested. A high proportion of empirical antibiotic use based on clinical judgement was also reported in The Gambia among neonatal admissions , and elsAlthough the species for many of the organisms were not identified, the bacteria belong to the groups of the most dangerous resistant pathogens including both gram positive and negative organisms as reported by Fair et al. . They alThe possibility of missing data from the admission records especially the microbiology data makes it difficult to make absolute judgements on the use of antibiotics based on laboratory findings. The data we obtained from the laboratory could not resolve this problem because some of the records lack hospital numbers thus matching this data with the admission data was not feasible. Many of the organisms were reported as genus without identification to the species level, making it difficult to compare with other settings and specify the resistant organism more appropriately.Our study shows that more than half of the admitted patients received antibiotics although most of the available results showed no microbiological evidence for their indication, suggesting that most of the antibiotics were empirically prescribed. Although several other factors in such settings could contribute to use of antibiotics for patients without microbiological evidence, the availability of microbiology results was a useful guide for choosing the class of antibiotic. Thus, in addition to the use of standards to guide empirical antibiotic therapy such as that of the WHO, microbiological use to guide antibiotic prescribing should be encouraged. This is probably achievable through better access to laboratory services and the establishment of ABS and its promotion for acceptance. Our study has shown high bacterial resistance to commonly used antibiotics, including ESBL bacteria, warranting the need for further research on the local antibiotic resistance patterns of bacteria as well as setting up an antibiotic resistance surveillance system.


B. anthracis must take a course of antibiotics as postexposure prophylaxis (PEP) to prevent inhalation anthrax. During an anthrax event, public health authorities are responsible for conducting dispensing operations to offer PEP to exposed individuals. Jurisdictions have developed antibiotic PEP screening algorithms to determine which antibiotic is appropriate for each individual. Variability exists with regard to screening questions and dispensing decisions based on responses to those questions. It is likely that individuals with similar profiles will receive different antibiotics based solely on the jurisdiction in which they receive their PEP. This lack of consistency among jurisdictions may lead to a loss of confidence in the public health response among the public, the healthcare community, the media, and government leaders, which could compromise the response itself. We present New York City's planning assumptions, screening algorithm, a rationale for our screening questions, and our reasons for excluding screening questions asked by other jurisdictions. We hope that our efforts may assist others in developing and refining their algorithms and associated public messaging and encourage standardization with neighboring jurisdictions where appropriate.Individuals exposed to spores of  Individuals exposed to spores of B. anthracis must take a course of antibiotics as postexposure prophylaxis (PEP) to prevent inhalation anthrax, and public health authorities are responsible for conducting dispensing operations. Jurisdictions have developed antibiotic PEP screening algorithms to determine which antibiotic is appropriate for each individual. This article presents New York City's planning assumptions, screening algorithm, a rationale for screening questions, and reasons for excluding screening questions asked by other jurisdictions. The identification and treatment of ill individuals, communication with the public and local stakeholders , and the dispensing of antibiotics and vaccine as postexposure prophylaxis (PEP) to all potentially exposed individuals must be considered.PDepending on the location, quantity, and mechanism of an anthrax release, thousands to millions of people from many jurisdictions may be exposed and require PEP. These individuals will need to obtain PEP from points of dispensing (PODs) or other dispensing options operated under the jurisdiction of state and local health authorities.1 Therefore, variation exists among these algorithms with regard to screening questions and the dispensing choices based on responses to those questions. Given this variation, it is highly likely that clients with similar profiles will receive different antibiotics based solely on the jurisdiction in which they receive their PEP. While this fact may not adversely affect the desired outcome of prevention of inhalation anthrax, such inconsistency is likely to erode trust in the public health response among the public, the healthcare community, the media, and government officials and lead to confusion and perceptions of inequity, both of which could negatively affect compliance with public health recommendations and adherence to the full PEP regimen.State and local public health authorities throughout the United States, including the New York City Department of Health and Mental Hygiene (DOHMH), have developed screening algorithms to determine what type of antibiotic PEP is dispensed to clients in response to an anthrax attack. Yet, as has been described, these were developed using general guidance, but not specific recommendations, from federal health authorities.Each jurisdiction must, when developing its algorithm, incorporate evidence-based principles , inventory concerns , and operational considerations . In this article, we present New York City's anthrax antibiotic screening algorithm for a deliberate anthrax release, discuss the rationale for our choice of screening questions, including our rationale for excluding some common questions, and describe how we intend to handle clients who require additional medical evaluation. This article does not address screening or other considerations related to the administration of anthrax vaccine.B. anthracis immediately begin a 60-day course of an oral antibiotic and a 3-dose course of anthrax vaccine for PEP. Doxycycline and ciprofloxacin are FDA approved as equivalent first-line antibiotics for PEP as they are equally effective and have similar susceptibility profiles among naturally occurring B. anthracis isolates.3 Clindamycin or amoxicillin is recommended for individuals who have an allergy or other contraindication to both doxycycline and ciprofloxacin, although neither is FDA approved for anthrax PEP.4 Jurisdictions rely on the CDC's Strategic National Stockpile (SNS) for the antibiotics necessary for large-scale PEP operations.5The Centers for Disease Control and Prevention (CDC) recommends that all individuals exposed to spores of 6 The DOHMH relies primarily on a neighborhood-based POD network to dispense PEP. While the vast majority of staff in NYC PODs are nonclinical, there are clinical staff at each POD in the medical evaluation unit.The DOHMH is assigned the core competency of mass prophylaxis/vaccination in the New York Citywide Incident Management System (CIMS) and is therefore authorized to direct such operations in New York City.1.New York City will receive doxycycline and ciprofloxacin from the SNS in quantities that are sufficient for large-scale dispensing at PODs;2.B. anthracis will be susceptible to both of these first-line antibiotics;The strain of 3.We may receive quantities of ciprofloxacin suspension and amoxicillin from the SNS, but these quantities will be insufficient for allocation across a large network of POD sites to ensure availability at all sites given variable rates of consumption;4.Antibody-based options for anthrax PEP  are not considered suitable options for consideration at PODs as they are administered by infusion in a healthcare setting;5.Clients who must take ciprofloxacin suspension, amoxicillin, or clindamycin can be directed from a POD to a local pharmacy; and6.a.Supplies of ciprofloxacin suspension, amoxicillin, and clindamycin in the commercial supply chain are limited; andb.Clients will experience delay in beginning their PEP as opposed to those who receive antibiotics in a POD.The number of clients directed to a local pharmacy should be minimized:In the development of our plan, we have assumed that:A screening form with the following questions must be completed for each individual receiving antibiotics for anthrax PEP. The DOHMH has a designee pickup policy that allows a client to present completed screening forms for him- or herself and up to 5 other individuals at a POD. Clients are provided with an explanation of each question to assist them in answering the question correctly. [Note: These questions and explanations have been translated into the 12 most commonly spoken languages in NYC and are available upon request.]1.Has the person who will take the antibiotic ever had a severe allergic reaction to doxycycline or tetracycline antibiotics that required medical attention?2.Is the person who will take the antibiotic pregnant?3.Has the person who will take the antibiotic ever had a severe allergic reaction to ciprofloxacin (Cipro) or other fluoroquinolones that required medical attention?4.Does the person who will take the antibiotic have myasthenia gravis?5.®)?Is the person who will take the antibiotic taking tizanidine  has listed doxycycline and ciprofloxacin as Pregnancy Categories D and C, respectively,The DOHMH will not dispense doxycycline to clients who answer “Yes” to this question unless they also answer “Yes” to any of questions 3 through 9. These clients will be referred to medical evaluation, where they will receive doxycycline or a prescription for an alternative antibiotic if they answer “Yes” to question 1.Has the person who will take the antibiotic ever had a severe allergic reaction to ciprofloxacin (Cipro) or other fluoroquinolones that required medical attention?3. 8 The DOHMH will not dispense ciprofloxacin to clients who answer “Yes” to this question.Ciprofloxacin is contraindicated in individuals who have shown hypersensitivity to any of the fluoroquinolones.Does the person who will take the antibiotic have myasthenia gravis?4. 8Myasthenia gravis is a neuromuscular disease that is characterized by fluctuating muscle weakness and fatigue. The FDA has issued a black box warning that ciprofloxacin may exacerbate muscle weakness in people with a history of myasthenia gravis.12 serious morbidity  or mortality may occur in people with exacerbation of disease.While myasthenia gravis is relatively uncommon and has an estimated prevalence of ∼20 per 100,000 people in the United States,The DOHMH will not dispense ciprofloxacin to clients who answer “Yes” to this question.®)?Is the person who will take the antibiotic taking tizanidine . These clients will be referred to medical evaluation, where they will receive ciprofloxacin (if they have not indicated they have another contraindication to ciprofloxacin), be advised to take their first dose, and then to immediately contact their dialysis center, nephrologist, or other healthcare provider to determine whether they should adjust further doses of ciprofloxacin.Is the person who will take the antibiotic unable to swallow pills?8. Individuals who are unable to swallow pills must take a liquid form of either doxycycline or ciprofloxacin. Doxycycline can be crushed and mixed with food or drink, and DOHMH will make crushing instructions available to those who need them. The FDA has not issued crushing instructions for ciprofloxacin because of concerns that the extreme unpalatability of crushed ciprofloxacin will adversely affect adherence.DOHMH will not dispense ciprofloxacin to clients who answer “Yes” to this question unless they also answer “Yes” to question 1 . For those clients, medical evaluation staff will provide a prescription for ciprofloxacin suspension.Does the person who will take the antibiotic weigh less than 76 pounds or 35 kilograms?9. 7 Doxycycline may be crushed and mixed with food or drink to ensure that the client receives the appropriate dose. Instructions on crushing doxycycline will be made available to POD clients.Individuals who meet this criterion and who can take doxycycline should take less than the adult dose.8DOHMH will not dispense ciprofloxacin to clients who answer “Yes” to this question, as it may not be crushed (see question 8 above), unless they also answer “Yes” to question 1 . For those clients, DOHMH will dispense ciprofloxacin to those who weigh between 67 and 76 pounds and have answered “No” to question 8 . Medical evaluation staff will provide a prescription for ciprofloxacin suspension to those weighing less than 67 pounds.We have reviewed screening forms and algorithms from other health departments, including examples developed by other large cities with demographics similar to New York City as well as those from smaller jurisdictions. During our review, we noted that some questions are standard on all forms , but there is variability regarding other questions . We opted to exclude a number of questions that are asked by some other jurisdictions. As discussed previously, under ideal circumstances, some clients should not take either doxycycline or ciprofloxacin. However, these antibiotics will be immediately available in a POD, and, due to the emergent nature of an anthrax emergency, the likelihood of a severe outcome from inhalation anthrax, and the delay clients will experience obtaining an alternative antibiotic from a local pharmacy, we have chosen not to include questions regarding non–life-threatening adverse drug reactions to either antibiotic. In an attempt to further reduce risk from PEP-related adverse events, our public messaging will encourage clients who meet various criteria  to consult with their physician once they begin their PEP. Our rationale for not including these screening questions is described below.Questions regarding seizure disorder/epilepsy1. 8 This effect may increase the risk of seizure in individuals with seizure disorder, including epilepsy. Ciprofloxacin-associated seizures have been described in patients with certain risk factors, including advanced age and renal insufficiency.14Doxycycline and ciprofloxacin, as well as antibiotics from other classes, may lower the level of various anti-seizure medications.Neither doxycycline nor ciprofloxacin are without risk in these individuals, and medical evaluation staff will lack the means to more fully evaluate individuals with seizure disorders.Screening for this condition is unlikely to influence the choice of antibiotic in a POD setting.Questions regarding a history of tendon rupture2. 8 This adverse reaction most frequently involves the Achilles tendon but may also involve the rotator cuff, hand, biceps, thumb, and other tendons. The risk of these adverse reactions is increased in individuals over 60 years of age, in patients taking corticosteroids, and in people with kidney, heart, and lung transplants. However, a history of tendon rupture is not considered a contraindication for ciprofloxacin.The FDA requires a black box warning that ciprofloxacin has been associated with an increased risk of tendinitis and tendon rupture.Screening for this non–life-threatening condition may lead to an increase in individuals who require a prescription for an alternative antibiotic.Questions regarding breastfeeding3. 8 The amount of either absorbed by the nursing infant is unknown. There is a potential for serious adverse reactions in infants nursing from mothers taking either of these antibiotics. Neither antibiotic has been shown to create more risk than the other.Both doxycycline and ciprofloxacin are excreted in human milk.Screening for breastfeeding is unlikely to influence the choice of antibiotic in a POD setting.Questions regarding chemotherapy agents4. 8Interactions between both doxycycline and ciprofloxacin with methotrexate have been reported. There is a potential for an interaction by both antibiotics with other chemotherapeutic agents.Screening for use of chemotherapy agents is unlikely to influence the choice of antibiotic in a POD setting.Questions regarding anticoagulant drugs5. 8 and individuals taking anticoagulants concomitantly with one of these antibiotics should monitor their prothrombin time and INR accordingly.Both doxycycline and ciprofloxacin can affect an individual's response to anticoagulant drugs,Screening for use of anticoagulant drugs is unlikely to influence the choice of antibiotic in a POD setting.A client directed to medical evaluation will consult with a licensed physician, nurse practitioner, or other clinician who has authority to prescribe antibiotics. The clinician will review the client's answers to all 9 questions, with particular attention to any “Yes” response, in order to determine the validity of the client's answers. As an example, a client may indicate that he or she has had a serious allergic reaction to doxycycline, which, after evaluation by a clinician, is not actually supported by the person's history.Medical evaluation staff will follow a standardized procedure to conduct their review and will determine whether a client should receive doxycycline or ciprofloxacin at the POD, or ciprofloxacin suspension or an alternative antibiotic recommended by CDC for use as anthrax PEP. Medical evaluation staff will provide a prescription for ciprofloxacin suspension or an alternative antibiotic for the small number of clients who require these options and direct them to a retail pharmacy.We have presented our planning assumptions, anthrax antibiotic screening algorithm, our rationale for our choice of screening questions, and our medical evaluation function. The screening algorithm has been integrated into current NYC DOHMH policy and is regularly used in our POD leadership training.We hope that this article will assist responders in preparing for and responding to an anthrax emergency and that they will consider standardizing their screening algorithms with neighboring jurisdictions whenever possible. We understand that some jurisdictions may not operate under the same assumptions as NYC . However, a thorough consideration of these possible variables in advance of an anthrax emergency will enable local planners to incorporate those assumptions into their plans and be better prepared to explain differences, if necessary, at the time of a response with clear, aligned messaging.We strongly believe that a consistent, evidence-based antibiotic screening approach will maximize public trust, promote efficiency at PODs, and increase the likelihood of a successful response to a large-scale anthrax event.


Clinical practice guidelines produced by developed countries seemed to be not completely feasible for developing countries due to their different local context. In this study, we designed a customized guideline about antibiotic prophylaxis before dental procedures for Iranian general dentists.This study was conducted of two parts, including a qualitative part and a cross-sectional analytic part. A multidisciplinary team searched for related guidelines and other documents, selected the most updated and high quality ones, customized their recommendations based on available antibiotics in Iran, prepared a draft adapted guideline and summarized its recommendations in 3 flowcharts. An expert panel  participated in a consensus process, afterwards to determine the relevance and clarity of the flowcharts and their items. Then the Content Validity Indices (CVIs) were calculated and any items with CVI higher than 0.79 remained.The adapted recommendations were summarized in flowcharts A to C. Two separate groups of patients who need antibiotic prophylaxis were presented in flowchart A; including those with high risk for distant-site infection (infective endocarditis and prosthetic joint infection) and those at risk for poor healing and orofacial infection (due to impaired immunologic function). Flowcharts B and C described antibiotic regimen and also the dental procedures where antibiotic prophylaxis was needed for mentioned groups. The content validity indices and the percentages of agreement between the expert panel members were considerably high.A localized, clear and straight forward guideline that addresses all groups of dental patients who need antibiotic prophylaxis has been produced for Iranian general dentists.Supplementary information accompanies this paper at 10.1186/s12903-019-0905-3. Deciding about the best prescription for patients might be confusing. Clinical practice guidelines (CPGs) provide evidence based recommendations to help practitioners select the best treatment plan and the most effective drug regimen. Some international organizations and developed countries have already prepared and asserted several CPGs , 2. HoweAntibiotics are one of the most common medications prescribed by dental practitioners . They arAntibiotic prophylaxis (AP) has been considered to be safe and cost-effective. Dental practitioners have welcomed antibiotic prophylaxis regimen partly due to the fear of being blamed. However, they have also been confused about the correct prescription at the same time, as they do not deal with such patients as a routine manner.The main potential problems of widely using AP are risk of adverse drug reactions, costs for the health-care system and risk of promoting antibiotic resistance , 21. AltVariations in antibiotic resistance between countries can be attributed to different volumes and patterns of antibiotic consumption, whether this use is appropriate or not , 27. DueTherefore, there is a need to a readily accessible, problem-orientated CPG which should be matched with each community population’s needs. Therefore, the aim of this study is to design and adapt a guideline about AP, giving Iranian general dentists the recommendations on when, which and in what dosage the antibiotics should be prescribed.This study consisted of a qualitative part and a cross-sectional analytic part. It was carried out during the three main phases   by a mulTwo themes were considered in advance for searching CPGs and other documents. One theme investigated AP in different group of patients including those with cardiac conditions, with prosthetic joints and with impaired immunologic functions. The other theme considered AP for adults and children, separately. Since CPGs might not be published in journals; we started the search for guidelines about AP since 2005 in guideline clearinghouses such as the National Institute for Clinical Excellence (NICE), the American Dental Association (ADA), the Royal College of Surgeons, the Scottish Dental Clinical Effectiveness Program, etc.An additional search in a broader database such as MEDLINE, Springer, Elsevier and Cochran Library using a standardized search strategy was done for more guidelines. Following terms were used: practice guideline [Publication Type] OR guideline [Title], in combination with words related to antibiotic prophylaxis [Title] AND dental care OR dentistry OR Infective Endocarditis OR Prosthetic joint OR immunosuppression OR immunocompromised patients. Internet search engines such as Google and Yahoo were also used to find guidelines. A recent study indicated that available CPGs on the Internet had equal or higher quality than those published in the periodical literature . A furthThe following characteristics of the retrieved CPGs were summarized in a table: developing organization/authors, date of publication, country/language of publication and the practice guideline’s recommendations. Those CPGs which were not in English language, or were based on approvals made before 2005, and those which were outdated by a later update of the same organization were excluded.The focus group was asked to discuss and write their opinions about selected guidelines and recommendations. The meeting was continued until a clear conclusion was obtained. The final recommendations were attained using content analysis and coded by one calibrated coder. All transcripts returned to multidisciplinary team for comment and/or correction. The recommendations were subsequently localized based on available antibiotic forms in Iran. Antibiotics’ forms and dosage were checked by pharmacologists of Food and Drug Department of Shiraz medical university. The draft of all customized recommendations and related data were prepared and summarized in the Flowcharts A to C  was asked to recommend five dental specialists among Iranian university professors. Due to three duplicate names among the twenty-five introduced professors, twenty-two ones were invited for expert panel. All invited participants were informed about the study’s aim, scope and process, and the interests of the interviewer, by written materials printed and sent to them. Verbal discussion over phone or in person was followed when necessary. Since two of the specialists refused to participate in the consensus process, the study was continued with twenty ones. The selected dental specialists including 2 dental public health specialists, 5 oral medicine specialists, 3 oral and maxillofacial surgeons, 3 periodontists, 3 endodontists, 1 pediatric dentist, 1 orthodontist, 1 prosthodontist and 1 restorative specialist were from four Iran universities . Written informed consent was obtained from each participant in advance to their participation. All meetings were conducted in dental schools.Three questionnaires were designed to assess the relevance and clarity of different items of flowcharts. The questionnaires consisted of 6, 12 and 14 questions for flowcharts A, B and C, respectively. A 4-point ordinal scale was considered for each question to avoid a neutral midpoint . Labels The expert panel was asked to determine the relevance and clarity of each item by selecting one of a 4 point ordinal scale and to write any revision if needed based on their knowledge and experience. The Content Validity Index (CVI) , 40–42 wIn the last phase, all flowcharts were re-evaluated; any items with CVI higher than 0.79 were remained  and any Twenty two guidelines and systematic reviews were obtained as search results. Five guidelines were excluded and seventeen most recently updated guidelines and systematic reviews which were fully available, had structural soundness and met our inclusion/exclusion criteria were selected and used in this study. The results of adapted recommendations were summarized in Flowcharts A to C  due to lack of evidence for association between dental procedures and the occurrence of PJI . HoweverThere are many medical conditions associated with suppression of the immune system including some underlying diseases and medication for managing these diseases . Since sThe results of content validity tests of the mentioned flowcharts are presented in Tables For the 12-item Flowchart B, 99 and 100% of experts determined items as relevant and clear, respectively. About 83% of items achieved relevance rating of 3 or 4 by all experts; while for the clarity, the universal agreement of 100% was obtained. Table The present study customized the recommendations of updated CPGs regarding AP for Iranian general dentists. Several guidelines including those from the American Heart Association (AHA) , the AmeAlthough other guidelines about AP existed for specific groups, the flowchart presented in the current study would be one of the few guidelines which presented all groups who need AP together. Any dentist, a general practitioner or specialist, can simply use these flowcharts. Using Flowchart A, the two distinct groups who need AP can easily be distinguished. The dentist can easily move to Flowchart B or C, afterwards and follow the instructions for prescribing the AP.The present study suggested that the antibiotic regimens supported by the AHA for cardiac indications might be appropriate for preventing PJI (Flowchart B) in all susceptible patients. The underlying mechanism of bacteria spreading from mouth to prosthetic joints (PJ) was the same as IE, though the anatomy, microbiology and pathogenesis of PJI and IE were different . FurtherRecommended prophylactic antibiotic regimens in this study are all based on nationally available forms of antibiotics in Iran. For Amoxicillin for example, four 500 mg capsules are stated in the flowcharts as this is the most available form of this antibiotic. This is while in some countries like the UK, there are ready-to-use sachets of Amoxicillin powder . FurtherProphylaxis was considered reasonable for both groups of patients mentioned in Flowchart A before invasive dental procedures which manipulated the gingival tissue or the periapical region of teeth or perforated the oral mucosa , 50, 52.The present study introduced a national and adapted guideline regarding AP for Iranian general dental practitioners. The introduction of antibiotic prescribing guidelines in England could improve general dentists’ practice in antibiotic administration and reduce the number of inappropriate prescriptions . ExpressTo move towards evidence-based practice in developing countries, it is better to emphasis on guideline adaptation and use rather than guideline development. Although guideline adaptation seemed simpler than guideline development, it was a complex time-consuming process (12 to even 24 months) needing more resources, support and facilitation than expected. Advanced methodological skills would be required to find and to appraise high quality documents. Furthermore, one favorable feature of the present guideline was diverse composition of the multidisciplinary team and the expert panel. Although this diversity led to more difficulties in arrangements, it played an important role to participate all involved specialists of dental universities’ departments in the process of guideline adaptation. The recommendations of this guideline were based on high levels of scientific evidence as well as complete consensus of the expert panel. Therefore, these recommendations, presented as flowcharts, could be confidently recommended for Iranian general dentists. It is important to remember that guideline adaptation was not an episodic activity and planning for periodically updating should be considered in all communities.In the present study the recommendations retrieved from updated CPGs regarding AP, were adopted and were converted to simple flowcharts for easier and faster access of Iranian general dentists. The flowcharts contained information about two distinct groups of patients who need AP, the antibiotic regimen for both adults and children and the dental procedures for which AP should be recommended. Relevance and clarity of the overall flowcharts and their items were evaluated by an Iranian expert panel. High content validity for the flowcharts was obtained and high percentages of agreement between the experts were reported.Additional file 1: Our recommended flowchart for antibiotic prophylaxis for Iranian general dentists based on available antibiotics in Iran- Part A. (PDF 250 kb)Additional file 2: Our recommended flowchart for antibiotic prophylaxis for Iranian general dentists based on available antibiotics in Iran Part B: patients at high risk for distant-site infection. (PDF 355 kb)Additional file 3: Our recommended flowchart for antibiotic prophylaxis for Iranian general dentists based on available antibiotics in Iran Part C: patients at risk for poor healing and orofacial infection (Due to impaired immunologic function). (PDF 357 kb)