Anaplasma spp. in goats in Chattogram district, Bangladesh.Anaplasmosis is an economically important disease affecting cattle, buffalo, sheep, goat etc. The study was conducted to determine the prevalence, potential risk factors and molecular identification of circulating Anaplasma spp.Four hundred blood samples were collected from goats of different ages, breeds, sex, coat color and body condition. These goats were selected based on some inclusion criteria through the period of July 2017 to June 2018. Samples were examined microscopically (Giemsa staining method) followed by polymerase chain reaction (PCR) and sequencing to identify of Anaplasma ovis (A. ovis) and Anaplasma marginale  were identified with the prevalence of 14.75% (59/400) and 1.0% (4/400), respectively through PCR. Among different risk factors, jamnapari breed (p = 0.027), no use of acaricide (p = 0.025) and presence of tick (p < 0.01) were found to be significantly associated with anaplasmosis. Sequence analysis of msp4 gene revealed that, Anaplasma spp. detected in the present study were highly similar with those of China, Venezuela, Mongolia, Spain, Tunisia, Cyprus, Italy, Brazil, Argentina, Australia, Japan and Columbia.The overall prevalences were estimated 5.75% (23/400) and 15.75% (63/400) by microscopy and PCR, respectively. In conclusion, strategic use of acaricide can control tick that ultimately will control the anaplasmosis in goats. Besides, rearing local goats in compare to cross and exotic breed are also recommended for the farmer to prevent the disease. Anaplasma ovis and Anaplasma marginale were identified as 14.75% and 1.0%, respectively, through PCR. Tick infestation on goats and no use of acaricide were identified as significant risk factors for anaplasmosis.The overall prevalence of anaplasmosis in goats was estimated 5.75% and 15.75% by microscopy and PCR, respectively, in this study.  Chattogram is located in south‐eastern part of the Bangladesh. Its area is 5282.98 sq km, located in between 21°54' and 22°59' north latitudes and in between 91°17' and 92°13' east longitudes. It is bounded by Khagrachhari and Rangamati districts and Tripura state of India on the north, Cox's Bazar district on the south, Bandarban, Rangamati and Khagrachari districts on the east and Noakhali district and the Bay of Bengal on the west. It consists of 14 Upazilla (Administrative locations) and Chattogram Metropolitan Area. The tropical monsoon climatic condition characterises by annual average temperature of 132.2N is required sample size, Pexp is expected prevalence = 50% = 0.5 , d is desired absolute precision = 5% = 0.05, 1.96 is the value of z at 95% confidence intervalThe study was conducted from July 2017 to June 2018. The study population was goats that were visited to the Teaching Veterinary Hospital from different area of Chattogram district for the purpose of health check up, vaccination, deworming and treatment of illness. Immediately after registration, clinical history was taken and physical examination was performed for each goat. Physical examination included observation of general appearance, examination of backbone and ribs, observation of visible mucous membrane, palpation of superficial lymhnode, recording of body temperature etc. Goats more than 6 months old that had at least one or more following criteria like presence of vector ticks on the body, fever, anorexia, anaemia, swollen lymphnode and jaundice were considered for sample collection. Based on these criteria, the required numbers of study goats were selected. Sample size (numbers of goats) was determined by the following formula , age category , sex , body color , body condition score , different management system like rearing system , grazing  and flock size , acaricide using history (yes or no), presence of tick on the body surface (yes or no) and date of registration were recorded using a close ended questionnaire by face to face interview of owner and close examination of goat. After that, blood sample (5 ml) was collected from jugular vein of each goat using sterile disposable needle. Before collection, the puncture area was cleaned and disinfected with 70% alcohol. Thin smear was prepared using a drop of blood on a slide. After labelling, slide was air‐dried and fixed in methyl alcohol. Remaining blood was transferred into vacutainer containing anticoagulant (EDTA) and transported to the laboratory for further analysis Kessell, .2.3Anaplasma inclusion bodies under light microscope.The fixed thin smears were stained with Giemsa stain at a dilution of 10% in buffer solution and allowed to stay for 20 min followed by washing with tap water to remove extra stain. Then the slides were air dried and examined for the presence of 2.4®, Korea) was used to extract DNA according to the manufacturer's instructions. Briefly, 20 μl of proteinase K solution was added to 1.5 ml micro‐centrifuge tube containing of whole blood sample (200 μl). Then binding solution (200 μl) was added to the same tube and thoroughly mixed (vortexing for 15 s) followed by incubation at 56°C for 10 min. After incubation, absolute ethanol (200 μl) was added and mixed similarly for 15 s. The lysate was carefully transferred into the upper reservoir of the spin column and centrifuged at 13,000 rpm for 1 min. After discarding the flow through, column was washed two times with 500 μl of washing solution 1 and washing solution 2 by centrifugation at 13,000 rpm for 1 min each time. After washing, column was dried by additional centrifugation at 13,000 rpm for 1 min to remove the residual ethanol of spin column. Finally, spin column was transferred to the new 1.5 ml Eppendorf tube and genomic DNA was eluted with 100 μl of elution buffer by centrifugation at 13,000 rpm for 1 min and stored at –20°C for further analysis.Genomic DNA Extraction Kit , 53°C for 1 min  and 72°C for 1 min (extension step) with a final extension step for 72°C for 7 min. After amplification of 16SrRNA gene, only samples positive for 16SrRNA gene were further amplified for msp4 gene to confirm A. ovis/ A. marginale. Initialy, msp4 gene was amplified with A. ovis specific primer in an initial denaturation at 95°C for 5 min followed by 30 cycles at 94°C for 30 s (denaturation step), 60°C for15 s  and 68°C for 30 s (extension step) with a final extension step for 68°C for 5 min. After that, only samples negative for A. ovis specific primer amplifications were subjected to amplification of msp4 gene with A. marginale specific primer in an initial denaturation at 95°C for 5 min followed by 30 cycles at 94°C for 30 s (denaturation step), 58°C for 15 s  and 68°C for 30 s (extension step) with a final extension step for 68°C for 5 min. In 16SrRNA gene amplification both positive and negative control and in msp4 gene amplification only negative control were used. The PCR products were analyzed in 1.5% agarose gel in 0.5 TAE buffer and visualised in ethidium bromide and UV transilluminator. The details of primer mentioned in Table PCR amplifications were carried out using a 2720 thermal cycler . It was performed in a total volume of 20 μl for each reaction using mastermix 10 μl), 10 pmol primer (1 μl for each primer), DNA template (4 μl) and nuclease free water (4 μl). Mastermix includes 20 mM Tris‐HCl (pΗ8.8), 100 mM KCl, 0.2% Triton0 μl, 10 2.6A. ovis and two from A. marginale) were purified using commercial PCR purification Kit  following the procedures described by the manufacturer. Briefly, 40 μl of PCR product was mixed thoroughly with 200 μl of FADF buffer by vortexing. The mixture was then transferred to a FADF column and centrifuged for 1 min and the flow through was discarded. Wash buffer (750 μl) was added to the column and centrifuged for 1 min. After discarding the flow through the column was centrifuged again for 3 min to dry and placed on a new microcentrifuge tube. Elution buffer (40 μl) containing 10 mM Tris‐HCl (pH 8.5) was added to the column and incubated at room temperature for 2 min. Column was then centrifuged for 2 min to collect the eluted DNA. Sequencing of purified PCR products were done by commercial sequencing company by conventional Sanger sequencing .Four PCR products (two from 2.7http://blast.ncbi.nlm.nih.gov/Blast.cgi) website. After that, we submitted our study sequences in GenBank and received the accession number. These were MN481609.1 and MN481610.1 for A. ovis and MN481607.1 and MN481608.1 for A. marginale. By the BLASTn homology search and sequences published in GenBank, nucleotide sequences were determined as corresponding to A. ovis and A. marginale. The multiple alignment and phylogenetic analysis was performed by Mega 10 software by Neighbor joining method  in compare to A. marginale  among the prevalence of Anaplasma sp.  and 15.75% (95% CI: 12.49–19.66) by conventional blood smear and molecular methods (PCR), respectively. The most prevalent infection was 3.2p < 0.05) associated with anaplasmosis  were considered in univariable logistic regression analysis. Among factors, breed, acaricide uses and tick infestation were found to be significantly (is Table  in goatsdy Table .p = 0.027) in univariate logistic regression analysis  and crossbreed  in comparison to Bengal goat  (p < 0.05)  than acaricide using goats . In both univariate and multivariate logistic regression analysis, odd ratio for using acaricides was 0.31 (95% CI: 0.09–0.81 and 0.09–0.84 respectively) (p < 0.01). The odd ratio was around 11.0  in both univariable and multivariable logistic regression analysis  in compare to non‐tick infested goats   and A. marginale (MN481607.1 and MN481608.1) showed 99% similarity at neocleotide level with isolates of different country that were previously submitted in GenBank database. The tree was constructed using the Neighbour Joining test and Mega 10 software. Sequence of A. marginale was used as outgroup for phylogenetic tree of A. ovis and vice versa. Topology of A. ovis tree shows the close relationship among A. ovis (MN481609.1 and MN481610.1) of this study and A. ovis from China (JN572931.1) because they positioned within same branch in the same cluster. The nearest relatives to the mentioned cluster are A. ovis from Mongolia (LC141086.1), Spain (GQ621903.1), Tunisia (KC432643.1), Cyprus (FJ460455.1), China (MG668814.1) and Italy (AY702924.1) and the lowest similarity was found with the isolate of A. ovis from Iran (KY091899.1)  of this study and A. marginale from Brazil (AY714546.1), Argentina (AF428087.1), Mexico (JN564652.1), Australia (AY666003.1) Japan (KU764497.1), Columbia (MF771052.1) and Venezuela (AY737009.1) are closely related. The next nearest relative sequences are A. marginale from Bangladesh (KX110079.1) and China (HM640938.1) that are clustered together. A. marginale sequence from Nigeria (EU106082.1) was found the lowest similarity with the A. marginale sequence of this study  found higher than the A. marginale (1.00%) which is in agreement with the findings of Yousefi et al. (A. ovis (34.6%) was higher than A. marginale (0.00%). Differences between two species may be due to variation of susceptibility of goats to A. ovis and A. marginale. However, the prevalence of A. ovis (14.75%) of this study was inconsistent with the findings of Yousefi et al.  and in summer (17.29%) than the rainy (12.85%) season though they were not statistically significant. Similar seasonal variation was also observed by previous investigators both in goats and cattle, reported higher incidence in winter season Mannan,  reportedAnaplasma infection found in extensive (17.64%) than intensive (16.17%) and backyard farming (15.30%). This finding concurs with previous findings of Angwech et al.  than non‐grazed (16.21%) animal and which is supported by the findings of Rajasokkapan and Selvaraju (2016) who found that tick‐borne diseases found higher in animal grazed in pasture than non grazed. The extensive system of rearing animal used to graze in pasture has direct effect on tick‐borne diseases as possibility of vectors exposure from nature become higher.In univariate and multivariate logistic regression analysis, higher risk of h et al.  and Wesoh et al.  where thIn this study, goats from large flock (30.0%) showed more susceptibe than medium (20.0%) and small flocked goats (14.29%). Though these finding found statistically nonsignificant but supported by Kispotta et al.  and Shahp = 0.027). Higher infection was recorded in jamnapari (23.52%) followed by crossbreed (22.31%) and black Bengal goats (12.21%), respectively. Similarly, Siddiki et al.  than the male goats (15.23%) which was consistent with Yousefi et al.  in goatsGoats less than 1 year old were found in more risk for anaplasma infection in comparison to other age groups. This observation was statistically nonsignificant and was opposite to the finding reported in India . The variation of risk in age category could be due to disproportionate sampling of the study.Body condition score disclosed nonsignificant association of occurrence of anaplasmosis in goats in this study. As expected, poor (19.89%) body‐conditioned goats are more likely to get anaplasmosis than good (11.69%) body‐conditioned goats which is supported by previous studies  found more susceptible to anaplasmosis followed by black (15.43%), white (14.92%), brown (13.91%) and gray (12.50%) which was supported by Kispotta et al.  who mentThis study showed a significant association of anaplasmosis with the use of acaricide in goats. Goats not using acaricides were more likely to be positive for anaplasmosis than acaricide using goats. A similar observation has been reported by Kispotta et al.  in cattlp < 0.05). A similar observation was reported by Costa et al.    in their respective clade. This high value indicates that there is some genetic divergence among the isolates.A phylogenetic tree was constructed by the Neighbour Joining test using the Mega 10 software. The minimum similarity was seen for Yousefi,  and maxiYousefi, . The A. 5A. ovis and A. marginale were exist as both pathogenic and subclinical form. Different breeds of goats, no use of acaricide and presence of ticks on host were found as significant risk factors for anaplasmosis in goats. Sequence analysis revealed that isolates of the study were identical to the isolates reported from countries like Iran, Venezuela, China, Hungary, Japan, Italy, Brazil, Mexico, Australia and the United States. In context of our study, it is highly suggestive for the farmers to rear local breed in compare to exotic and crossbred to prevent the disease. Besides, regular acaricide practices are also recommended to control the tick as well as to control the disease.Anaplasmosis was moderately prevalent in goats of Chattogram region where The authors declare no conflict of interest.The study was conducted following approval from the Institutional Ethics Committee of Chattogram Veterinary and Animal Sciences University (CVASU), Chattogram, Bangladesh, protocol number: CVASU/Dir(R&E) EC/2020/165(4).MMR and MRF reviewed, designed and planed the study. MR was involved in sample collection, laboratory work, data analysis and initially drafted the manuscript. MYEC supervised the whole work. The manuscript was read and approved by each authors prior to submit.https://publons.com/publon/10.1002/vms3.775The peer review history for this article is available at


As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5–3.88 h landing time and/or 1–5.63 h probing time) and lower prices (13.9–21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents. Aedes albopictus is an important vector for the transmission of dengue viruses in mainland China, and females bite aggressively during the day and preferably outdoors [Ae. albopictus population than in other areas in China [Due to worldwide trade and global warming, mosquito-borne diseases have witnessed steady growth in the past few years and have caused epidemics around the world. The important mosquito-borne diseases are malaria, West Nile, yellow fever, dengue, chikungunya, and Zika . Owing toutdoors ,5. It hain China . These pin China . A majorTo control mosquito-borne diseases, many personal protection measures against mosquito bites have been suggested, such as wearing protection , mosquito nets, and the use of repellents. Given the unbearable heat in summer when mosquitoes are the most active, skin-applied repellents remained the first choice compared to wearing protection. Repellents are substances that are formulated for use on bare skin to help people avoid mosquito bites . The EnvThe research was limited to a full range of commercial mosquito repellents, usually of certain repellent ingredients in a specific country. The efficacy test of commercial repellents in China was a blank space. To fill this margin, we compared the repellent effect of 26 commercial skin-applied repellents on the Chinese market under laboratory conditions, and we also collected the price and high praise rate of mosquito repellents to make a more convincing recommendation of the best repellent product for Chinese consumers.Throughout 2021, the search index of mosquito repellents in China (Baidu index) reached its climax  in July . The salAe. albopictus bites. The DEET products (5–15%) provided a landing time ranging from 0.5 to 3.88 h and/or a probing time ranging from 1 to 5.63 h. The picaridin-based repellents (10–20%) provided a shorter landing time (ranging from 0–1.5 h) and/or shorter probing time (ranging from 0.5–2.5 h). The selected botanical products were non-repellent except ICE King, OMNIbaby, and Ren He. Products containing IR3535 (4.5–7%) provided only a landing time (ranging from 0–0.75 h) and/or probing time (ranging from 0.5–1.13 h)  against –1.13 h) .2 = 0.8751).Considering both the mean landing time and mean probing time, only 19 repellents showed repellency, and the top three repellents were Green Jungle (15% DEET), Bu Ding (15% DEET), and Ya Mei (10% DEET). Green Jungle (15% DEET), Bu Ding (15% DEET), and Ya Mei (10% DEET) showed repellent efficacy with a mean (±SD) landing time of 3.88 ± 1.65 h, 2.83 ± 1.75 h, and 2.50 ± 2.05 h and/or a mean (±SD) probing time of 5.63 ± 0.36 h, 4.80 ± 1.25 h, and 4.40 ± 1.14 h. Formulations containing 5% DEET  exhibited a different degree of repellency. Frog Prince presented the mean (±SD) landing time of 1.38 ± 0.48 h. Longrich and Coati had the mean (±SD) probing time of 1.75 ± 0.29 h. The mean landing time and/or probing time of 5%, 7%, 10%, and 15% DEET repellents were compared to determine the impact of concentration on mosquito repellency , but the probing time (mean (±SD), 2.5 ± 0.5 h) was longer . For the eight selected botanical products, only ICE King, OMNIbaby, and Ren He showed a little repellency against Ae.albopictus. ICE King had better repellency performance than the other two botanical products with a mean (±SD) landing time of 0.88 ± 0.25 h  and/or a mean probing time of 1.13 ± 0.25 h . Run Ben (7% IR3535) presented a similar landing time (mean (±SD), 0.75 ± 0.35 h) than other IR3535-based products (Matern’ella and Padano) , but had a longer probing time (mean (±SD), 1.13 ± 0.25 h) .The Autan (20% picaridin) had a similar landing time (mean (±SD), 1.5 ± 0.71 h) to the other two 20% picaridin products , Aerogard (10% picaridin), and five botanical products  were all non-repellent.Given that the favorable rates for Jingdong were all higher than 95%, which lacked comparability, we chose the favorable rates data from Taobao for analysis. However, the average price of each product was based on both Taobao and Jingdong for a fair result. In general, the prices of DEET, IR3535, picaridin, and plant component repellents were 13.9–21.9 yuan, 9.9–26.9 yuan, 28–48 yuan, and 12–39 yuan, respectively .Green Jungle (15% DEET), Bu Ding (15% DEET), and Ya Mei (10% DEET) had mean prices of 16.7 yuan, 21.3 yuan, and 30.3 yuan, respectively, with favorable rates of 95.55%, 95.77%, and 94.85%, respectively. Autan (20% picaridin) had an average price of 49.5 yuan with a mean favorable rate of 98.5%. ICE King  had a mean price of 24.0 yuan with a favorable rate of 94.45%. Run Ben (7% IR3535) reached an average price of 12.90 yuan with a favorable rate of 93.96% .Aedes, Anopheles, and Culex mosquito species for 6 to 13 h [Avoiding mosquito bites remains an important tool to cut off the transmission routes of mosquito-borne diseases. The application of effective mosquito repellents could avoid mosquito bites at lower costs. The mosquito repellents available are mainly based on DEET, IR3535, picaridin, and botanical components. Over the past decades, DEET has been a gold standard for repellents and is widely used. People tend to spray it on the skin or clothes to avoid mosquito bites. The mechanism of DEET repellent is to provide a vapor barrier that prevents mosquitoes from approaching the skin through the mediation of molecular targets (odorant receptors and ionotropic receptor Ir40a) . OdorantIn our study, DEET-based products provided the longest protection time (0.5–3.88 h landing time and/or 1.00 to 5.63 h probing time) at lower prices. The 5% DEET products had a moderate protection effect with the cheapest price (11.90 yuan), and even the 15% DEET, which provided the longest protection time throughout the test, was cheaper than picaridin and other repellents. Previous studies also indicated that the repellent efficacy of 23.8% DEET-based products was remarkable, with an average of 5 h of complete protection time at a single application .Although DEET has an excellent safety profile and remarkable protection against mosquitoes, its toxicity and ecological risk caused by incorrect use or overuse should be carefully discussed . DEET waAe. albopictus and higher prices but also possessed many advantages of an ideal repellent. It was odorless, had a better skin-applied feeling, and had less irritation with no damage to plastics or fabrics. However, there were limited picaridin-based commercial repellents on the Chinese market for testing. The 20% concentration of picaridin was considered to protect for up to 12 h against lone star ticks (Amblyomma americanum), which was similar to the protective effect of 33% DEET cream and much longer than the protection time of our tested repellents against Ae. albopictus [Ae. albopictus and was highly recommended for daily use.Picaridin had a shorter protection time against bopictus . In the From our study, full botanical products showed less repellency against mosquito bites than synthesized repellents, but certain components of the products received much attention from botanical repellent research. The main active components of botanical products were menthol and essential oils , which created a synergistic repellent effect. Citronella oil, an essential oil widely used in botanical products and a mixture of citronellal, citronellol, and geraniol, exhibited good efficacy under 100% concentration against mosquitoes in a study published in 2015 . The praAnopheles and Culex mosquitoes [Moreover, the repellent efficacy of a mixture of synthesized chemicals and essential oils might be higher than those of a single formulation. For instance, Green Jungle, consisting of lemon eucalyptus oil and 15% DEET, had a better repellent effect than the single 15% DEET product Bu Ding. Frog Prince, which mainly consists of plant extracts and 5% DEET, performed better regarding the landing time than other pure 5% DEET products, but the probing time of these 5% DEET repellents was very close. Padano, which had a 6% IR3535 blend formulated with botanical components, presented a better repellent effect than Ren He  but at a cheaper price. Some new botanical ingredients were reported to be included in the repellents, such as vanillin, liquid paraffin, and salicyluric acid . Formulasquitoes . Some bosquitoes .In addition, three famous traditional Chinese repellents  were also tested in the laboratory and showed less protective efficacy. In detail, both the cooling ointment and Liushen (gets rid of prickly heat) presented no repellence. The essential balm had a mean (±SD) landing time of 0.67 ± 0.29 h and/or a mean (±SD) probing time of 0.75 ± 0.35 h. Compared with the less effective traditional Chinese repellents, the formulations containing DEET, which have proven to be the best choice of repellents, were neglected by Chinese consumers, with only a medium sales ranking and an 87.99% favorable rate. Therefore, more information regarding the efficacy and safety of repellents is needed to guide consumers about the choice of mosquito repellents in China.IR3535 was not harmful when ingested, inhaled, or used on skin and did not accumulate in the environment. It was reported that IR3535 could increase nicotinic receptor sensitivity to the neonicotinoid insecticide thiacloprid by activating the orthosteric muscarinic receptor, which proposed a new approach to the integration of repellents . HoweverThe suitability and effectiveness of a repellent formulation depend on inherent properties such as vapor pressure, boiling point, and volatility . PreviouWith various kinds of repellents, consumers must make their own choices based on not only the repellent efficacy and price but also the occasions where repellents are applied. Symptoms of mosquito-borne illnesses in pregnant women usually manifest as pregnancy-specific illnesses, making treatment very difficult . For exaAe. albopictus were used for the efficacy test. Since certain repellents might show different repellent efficacy against different mosquito species, additional species could be included in this experiment. Only the skin of the hands was exposed to mosquitoes, which did not represent the other parts of the body in an outdoor environment. Because the concentrations of IR3535 and picaridin products were limited in the present Chinese market, the linear relationships between concentration and protection time were unable to be analyzed. Perhaps shortly more products of IR3535 and picaridin will emerge on the Chinese market.Although the data of this study were satisfying, some limitations still deserve to be discussed. The entire experiment was conducted in laboratory conditions with strictly controlled temperature and relative humidity, which could not fully simulate the real environment. A full-field or semi-field experiment was needed for further testing. In addition, to control the bias of the mosquitoes, only laboratory-reared DEET has played a leading role in commercial repellent products for many years, but there have been many new experiments on potential repellent compounds that are considered alternatives to DEET. For example, acylpiperidines were confirmed to provide repellency against mosquitoes by disrupting the insect olfactory system in 2020 . Some adFirst, we inquired about the search index of mosquito repellents in China throughout 2021 (Baidu index) to describe the repellent viewings by month. Next, the sales of repellent products in the highest-viewings month were collected from the commonly used e-commerce platforms Taobao and Jingdong. Last, the repellent products with high sales (>100) were included in the experiment .Ae. albopictus, collected from Foshan City in 1983, was used in this study. This mosquito was kept in the laboratory without insecticide exposure. All mosquitoes, including larval and adult mosquitoes, were maintained at 28 ± 1 °C and 80 ± 5% relative humidity under a photoperiod cycle of 14:10 h (light/dark) in the insectary.The Foshan  strain of Six adult volunteers  participated in the experiments. They were non-tobacco users and had no history of dermatosis or allergic reactions to arthropod bites or repellents. Given that various factors may alter a person’s attractiveness to mosquitoes, which may, in turn, affect the results of mosquito repellent tests, all the volunteers were required not to apply any aromatics, skincare, or other repellent products on the skin of the hands 12 h before and during the experiment. The experiment was approved by the Medical Ethics Committee of Anhui Medical University .Ae. albopictus females were conducted using the guidelines for the efficacy testing of mosquito repellents for human skin by the WHO [Ae. albopictus were placed in a net cage (40 × 30 × 30 cm) before the experiment. The tests were carried out between 15:00 and 20:00 h in accordance with the mosquito biting habits of Ae. albopictus in the 24-h cycle. Volunteers wore long-sleeve white coats to cover their arms, sterilized their hands and wrists with unscented soap, rinsed with water, rinsed with a solution of 70% ethanol or isopropyl alcohol in water, and put on gloves after drying hands with towels. Specific rubber gloves were designed to expose only a 4 × 4 cm area on the back of the hand skin  was used in the regression analysis. Given that the insertion interval was 0.5 h, a product was deemed non-repellent if the landing time was less than 0.5 h. The concentration of the main repellent components was included as an independent variable, whereas the complete protection time was included as the dependent variable in a linear relationship. The favorable rate of a repellent was calculated by the following formula:N is the number of consumers who gave a favorable reception to a repellent at one store, T is the total number of consumers buying this repellent in the store, and n is the number of stores selling the repellent on the e-commerce platform. The average price of repellents was also analyzed similarly.The data from the experiments were collected and analyzed to compare the repellent effect of different commercial repellent products against p < 0.05.Furthermore, a one-way ANOVA was applied to compare the landing time and probing time of different mosquito repellent products. All analyses were performed with IBM SPSS (v. 20.0), and significance was defined by The results from this study have demonstrated that DEET is still a gold standard of repellents with cheaper prices, proving more effective than the other commercial repellents marketed in China for protecting against mosquito bites. In general, Green Jungle (15% DEET) is most recommended for its powerful repellent efficacy and cheap price. Meanwhile, a majority of the botanical products tested are non-repellent and much more expensive than other products. However, the combination of botanical and synthesized chemicals presents a better effect than the single compound, indicating a new prospect for repellents. Given the features of different main components, Autan (20% picaridin) could be the substitute for DEET for those who cared more about skin feel. Run Ben (7% IR3535) is specifically suitable for younger children with safety concerns. However, further studies are required in the future with more kinds of repellents on the Chinese market, and the best choice of repellent may be replaced by more environmentally friendly products one day.


The aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods.We analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3).The RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34-4.10 mIU/L, 11.3-20.6 pmol/L, 3.5-6.32 pmol/L and 0.21-0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade , the fifth decade , the sixth decade , the seventh decade  and the group older than 70 years old . Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups.The establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations. To make an appropriate diagnosis of thyroid disease and for more cost-effective monitoring of patients with altered thyroid function, it is necessary to ensure a quality and accurate laboratory analysis of thyroid function parameters: thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3). TSH is the most sensitive marker for diagnosing subclinical functional thyroid disease. It is determined by the third generation methods with a sensitivity of 0.01 mIU/L i.e., values proposed by the manufacturer. Using accurate RIs (median with 2.5th or 97.5th percentile) is imperative for laboratory professionals because comparing individual results with RIs is crucial for medical decisions. The validity of RI for serum TSH primarily affects hypothyroidism's diagnostic accuracy.For these reasons, it is necessary to make reference values for one's own population and not to use external sources, The direct method for a RI calculation is a chiefly recommended technique Understanding the effects of within and between individual variability, analytical and preanalytical variability The goal of our study was to use indirect methods to estimate RIs for TSH, FT4, FT3 and FT3/FT4 ratio from results of the patients obtained during routine laboratory work. The investigation is conducted on the Republic of Srpska population.In this study, we analyzed the results of thyroid parameters  which have been collected from the laboratory information system (LIS) of the University Clinical Centre of the Republic of Srpska, Banja Luka. The measurements were performed on an ADVIA Centaur XP analyzer  using the chemiluminescent immunoassay (CLIA). The collection period for the analyzed thyroid parameters was from October 1, 2017, to April 1, 2021.The 1328 participants were enrolled in this study, older than 18 years, with predominantly female subjects (84%). The blood samples from outpatients were taken during the morning, between 7:00 and 11:00 a.m., at fasting. We excluded patients with positive antithyroid-peroxidase antibodies (>60 IU/mL) and antithyroglobulin antibodies . Only the first result of each patient was included.We evaluated patients' values within the RIs recommended by the manufacturer. Thus, when we estimate RIs for TSH, the FT4 and FT3 values should be within RIs but TSH values can be within, above or below RIs recommended by the manufacturer.Quality control was performed using corresponding commercial control samples with low, medium, and high concentrations. The limit of quantitation  of the ADVIA Centaur TSH3-Ultra assay was 0.008 mIU/L. Intra- and inter-assay coefficients of variation on the three levels of controls were for TSH 1.97%, 1.95%, 2.26% and 4.13%, 4.28%, 3.99%; for FT4 3.33%, 2.23%, 2.54% and 2.50%, 4.00%, 2.33%; for FT3 3.08%, 2.35%, 2.47% and 4.05%, 2.87%, 2.76%, respectively.The estimated parameters were included in the external quality assessment scheme . The RIs for TSH, FT4 and FT3 provided by the manufacturer were 0.55-4.78 mIU/L, 11.5-22.7 pmol/L and 3.5-6.5 pmol/L, respectively.th and 97.5th percentiles, were presented with 90% confidence interval (CI) for each limit. Considering Fraser's theory of »allowable bias« in laboratory tests, we tested whether the indirectly estimated RI significantly differs from the RI recommended by the manufacturer Reference limits (RLs) were determined using statistical programmes MedCalc, version 12.1.4.0  and SPSS version 24.0 . D'Agostino-Pearson test for normal distribution was used to test the distribution of the analyzed parameters. Suspected outliers were identified and omitted using the Tukey method Additionally, thyroid parameters were analyzed according to decades of life and presented as box plots. To reveal the significance of differences between the subgroups relative to decades of life, the ANOVA test with a post-hoc Tukey test was performed.In the Calculated RLs for FT3/FT4 ratio were: 0.21 (0.20-0.22) for 2.5th percentile (90% CI) and 0.47 (0.46-0.48) for 97.5th percentile (90% CI), with median value (90% CI) of 0.33 (0.325-0.335). Reference interval width for indirectly calculated vs. recommended reference limits was 3.76 vs. 4.23, 9.3 vs. 11.2, and 2.9 vs. 3.0, for TSH, FT4 and FT3, respectively . FurtherIn the next step, we analyzed parameters according to age groups Differences in the reference values for the analyzed thyroid parameters relative to the decades of life were estimated using the Tukey HSD post hoc test, as set in one way analysis of variance (ANOVA). First, we found an overall significance value for the difference between groups for TSH (F (5.1251)= 6.147, p<0.001), FT3 (F (5.1251)=12.015, p<0.001) and FT3/FT4 ratio (F (= 5.276) = 6.147, p<0.001). A Tukey post hoc test revealed that the TSH values were statistically significantly higher in the group younger than 30 years relative to the fifth decade , the sixth decade , the seventh decade  and the group older than 70 years old . Additionally, FT3 values were statistically significantly higher in the group younger than 30 years relative to the fourth decade , the fifth decade , the sixth decade , the seventh decade  and the group older than 70 years old . FT3/FT4 index was statistically significantly higher in the group younger than 30 relative to the fifth decade , to the seventh decade  and relative to the group older than the 70 years old .i.e. using data stored in our information system. There was a statistically significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. This indicates that it is necessary to define laboratory and method specific RLs for these thyroid parameters. The RIs for TSH in this study was apparently lower (0.34-4.1 mIU/L) than by the manufacturer (0.55-4.78 mIU/L). The RIs for TSH obtained on different populations, but the same analyzer  show differences in the lower and upper limit of RIs in the ranges from 0.32 to 1.01 mIU/L and 3.00 to 5.51 mIU/L, respectively In this study, we established reference values for TSH, FT4 and FT3 in the population of the Republic of Srpska by indirect method In addition, our results are more in line with the RIs population of the Republic of Serbia for TSH (0.35-4.10 vs. 0.42-3.67 mIU/L), if indirect method was used for determination of reference values According to ages, the shown changes for TSH are not clinically useful, which is in line with the results of other studies Surprisingly, both of our studies reported almost the same upper limit for FT4 and FT3 RIs (20.6 vs. 20.18 and 6.4 vs. 6.33 pmol/L), which to encourage us the future use of RIs obtained by indirect methods.The best compliance of our RIs with the proposed values by the manufacturer was for FT3 which is, ultimately, crucial for a complete assessment of the success of the therapy. In addition, this cross-sectional study indicates that FT3 values change with ageing. Therefore, the existence of an age-related decrease in the circulating FT3 levels might represent a physiological mechanism already shown in some studies The IFCC has so far made great efforts to standardize measurement for thyroid function tests, particularly for TSH, taking into account the different platforms used to measure these parameters. However uniform reference values for thyroid parameters have not yet been achieved. Therefore, routine clinical laboratories are advised to determine their own RIs following accepted consensus standards, such as those of the IFCC, National Academy of Clinical Biochemistry and CLSI Additionally, we have examined RLs for FT3/FT4 ratio as useful parameter to detect thyroid disfunction This study has some limitations, primarily the small number of male respondents in the research and no recent data on sufficient iodine.The establishing and using your own thyroid hormone RIs provides a much better basis for diagnosing or considering treatment for thyroid dysfunction than using a manufacturer interval. The our study indicates the need for greater use of the FT3/FT4 ratio in routine work. In addition, these results should encourage more laboratories to apply CLSI recommendations in determining RIs for thyroid parameters, for their specific populations.None.The authors reported no conflict of interest regarding the publication of this article.


Malaria is the leading vector-borne parasitic disease that is causing high morbidity and mortality worldwide. So far huge efforts to control and eliminate malaria are hindered by the occurrence of asymptomatic carriers that are a potential source of infection. Yet, there is a scarcity of data nationally and in the current study area as well. Therefore, this study was aimed to assess the prevalence of asymptomatic malaria in Northeast Ethiopia.A community-based cross-sectional study was conducted in 2019 involving a total of 270 study participants recruited via purposive non-probability sampling technique. A structured questionnaire was used to collect data on sociodemographic characteristics, individual and household factors related to asymptomatic malaria. Data were entered in Epi Data 3.1 version and analyzed by using SPSS version 20, and p< 0.05 was considered statistically significant.The overall prevalence of asymptomatic malaria was 7.0%, with 3.0%, 5.2%, and 12.0%, respectively by Rapid diagnostic tests (RDT), Microscopy and Polymerase chain reaction (PCR). The majority of infections (73.7%) were identified from index households. Previous malaria history , living with index cases  and family size > 6 members  were significant predictors of asymptomatic malaria.Reactive case detection had identified considerably higher asymptomatic malaria cases in the community. Therefore, active case investigation should be established in the community by tracking the symptomatic cases at the health facilities. Plasmodium, and transmitted through the bite of infected female Anopheles mosquitoes. Malaria is a serious public health problem in many parts of the world, exacting an unacceptable toll on the health and economic welfare of the world's poorest communities. Based on the WHO report, there were an estimated 228 million malaria episodes, and 405 000 malaria deaths in 2020, of which approximately 90% of the burden resided in Africa. Approximately 90 % of malaria deaths occurred in children under 5 years of age and pregnant women  are the most widely used diagnostic methods for clinical malaria and routine surveillance . HoweverMalaria control activities have substantially reduced malaria incidence over the last decade through different strategic interventions, including environmental management, indoor residual spraying, long-lasting insecticide-treated nets, and early diagnosis and prompt treatment . EthiopiThe presence of high prevalence asymptomatic carriage poses a threat to malaria elimination and control programs . Since aAnopheles mosquitoes increase in number by harboring the gametocyte stage to continue the cycle  of Ethiopia, the district had a total of 221,958 inhabitants  . The disStudy participants: The study participants for this particular research work were household contacts and neighbors of laboratory-confirmed malaria cases that lived at least for a year in the area. However, children below 6 months, individuals who had taken anti-malaria drugs within 4 weeks prior to data collection, and members of households and neighbors of laboratory-confirmed malaria cases with clinical signs and symptoms of malaria  were excluded.Sample size and sampling technique: A sample size of 270 was calculated using single population proportion statistical formula; by the following assumptions: 95% level of confidence, 3.5 % margin of error and P (proportion) of 95 % taken from a previous study , and household level factors  related to Plasmodium spp infection such as residence, family size via a face-to-face interview by the principal investigator.Blood sample collection, handling, and transportation: Finger prick blood specimen was collected for dried blood spot (DBS), RDT, and blood film. Three to four drops of blood were immediately spotted on Whatman 3MM filter paper for molecular analysis. The DBS was packaged individually into a double zip-lock plastic bag with desiccant and subsequently transported to Woldia General Hospital Laboratory for storage at - 20 °C. Later, it was transferred to Amhara Public Health Institute for PCR analysis.RDT  Ag Combo Test): After the pouch is open for immediate use, the collected capillary sample was blotted onto the sample pad of the test kit. Approximately, two drops of buffer were added onto the buffer pad and the result was read at the end of 20 minutes.Blood films: Both thin and thick blood films were prepared for the microscopic investigation of Plasmodium spp. The thin blood smear was fixed by carefully dropping methanol using a Pasteur pipette immediately after drying. The methanol-fixed thin smears were allowed to dry completely in the air (approximately 2 min) by placing the slides on a flat surface. The prepared blood smears were transported to the nearby health center in a slide box for Giemsa staining DNA Extraction: Briefly, three 3-mm punches of the DBS were punched out and placed into a 1.5-mL Eppendorf tube. The punches inside the Eppendorf tube were treated with ATL buffer, proteinase K, and AL buffer with brief vortex and incubation with respective addition. The mixtures were transferred into the QIAamp Mini spin column and with the subsequent addition of wash buffer AW1 and AW2. The DNA was eluted in 100 µL of elution buffer, aliquoted, and stored at -20°C until use.DNA amplification: Amplification of the Genus and P. falciparum multiplex was performed in a 20-ml reaction tube containing 10.0 µl 2X ABI TaqMan buffer, 0.5 µl each forward and reverse primer for the Genus, 0.5 µl forward and 0.25 µl reverse primer P. falciparum and 5 µl of DNA template. The reactions were performed under the following cycling parameters: initial hot-start at 95° C for 15 minutes, followed by 45 cycles of denaturation at 95 °C for 20 seconds, and 45 cycles annealing at 60 °C for 40 seconds. The correct fluorescence channel was selected for each fluorescently labeled primer set and the cycle threshold values were recorded at the end of the annealing step. Any sample with a cycle threshold value of 40 or below was considered positive. Both singleplex and multiplex assays were performed for all the samples  version 20  for analysis. Bivariable and multivariable logistic regression was performed to assess the association between the dependent variable and independent variables. Variables with a P-value of < 0.25 in the bivariable analysis were included in the multivariable logistic regression analysis. The odds ratio was calculated with a confidence interval of 95%, and a P-value < 0.05 was considered statistically significant.Socio-demographic characteristics: A total of 270 study participants residing in 60 households were enrolled in the study (72 from 20 index houses and 198 from 40 neighboring houses). The majority (61%) of the participants were female. The mean age of the participants was 21.02 (+18.6 SD) years. About 38.9%, 32.6%, and 17.0% of the participants were from Addis Kign Aradom, and Jarota  and P. vivax 42.1% (8/19) were identified in this study. All the 270 blood samples collected were tested for malaria via the rapid diagnostic test (RDT) and microscopy, yielding positivity rates of 3.0% (8/270), and 5.2% (14/270), respectively. However, only 92 samples were processed by the PCR method and it gave a prevalence of malaria at 12.0% (11/92). PCR detected asymptomatic malaria about 2.7-fold and 2.3-fold higher than RDT and microscopy, respectively  and Aradom (8.0%)  and 2.5% (5/198), respectively. The highest prevalence of asymptomatic malaria was recorded at two m (8.0%) .Plasmodium InfectionIndividual and Household Factors Associated with Bivariable and multivariable analyses: The bivariable analysis of individual and household factors showed a significant association with asymptomatic malaria at p-value <0.05. Consequently, age group > 15 years (COR: 3.1 [CI: 1.09–8.88]) and previous history of malaria (COR: 6.727 [1.912–23.668]) showed significant association with Plasmodium infection. Moreover, participants living in Addis Kign subdistrict (COR: 2.9 [CI: 1.11–7.66]), within index houses (COR: 5.5 [CI: 2.056–14.486]), and family size > 6 members (COR: 5.3 [CI: 5.291 (1.504–18.610]) were at higher odds of Plasmodium infection  with p ≤ 0.2 in the bivariable analysis were selected multivariate analysis to control confounder variables. After adjusting for confounders, only three variables  showed a statistically significant association with Plasmodium species infection (Eight predictors (age, relation with index cases, nfection .Plasmodium infection in individuals having previous malaria history was 4.0 times higher compared to those who didn't have it. Participants who lived in the index houses were at 3.9 times higher odds of getting Plasmodium infection than those who lived in neighboring houses. The odds of asymptomatic Plasmodium infection in households who had six or more members had 4.8 times higher than families with lower members (The odds of  members .Asymptomatic malaria becomes a serious challenge in malaria elimination. Individuals with asymptomatic malaria have low health-seeking behavior, and therefore, they remain potential reservoirs in sustaining malaria transmission .Plasmodium spp infection. This is in line with studies in Northwest Ethiopia 4.8%, (In the current study, RDT detected and identified 3% of the asymptomatic ia 4.8%, , Southeaia 4.8%, , Lao DPRia 4.8%, , and Haiia 4.8%, . On the ia 4.8%,  and Nortia 4.8%, . This diMicroscopy detected and identified 5.2% of asymptomatic infections. This is in line with studies done in Northwest Ethiopia 4.2% , 6.8% 2, WesternPlasmodium spp infections. This was higher than previous studies in Ethiopia; 8.12 % (PCR detected and identified 12% of asymptomatic ; 8.12 % , 18, Mya; 8.12 % , Zambia ; 8.12 % . However; 8.12 % , Haiti w; 8.12 % , Kenya; ; 8.12 % ,32, Indi; 8.12 % , and thi; 8.12 % . Therefo; 8.12 % .Plasmodium spp was P. falciparum with 57.9% and the remaining 42.1% was P. vivax. This finding is in line with the Ethiopian nationwide malaria figure reported by the Ministry of Health over which P. falciparum accounts for about 60% (P. vivax was the predominant species in Hadiya zone, Southern Ethiopia (Plasmodium species distribution as a result of environmental and ecological changes.This study also depicted that the predominant Ethiopia , and EasEthiopia . This diReactive case detection has identified a higher prevalence of asymptomatic infection in index houses with 19.4% compared with their neighboring houses with 3.5%. This finding is consistent with a study done in Jimma zone, Southwest Ethiopia . This diPlasmodium spp infection. This finding is supported by studies done in Ethiopia (P. falciparum in the circulation while relapse is due to the reactivation of hypnozoite which leads to initiation of the erythrocytic cycle in the case of P. vivax. However, these studies also underpinned living with index cases and family size > 6 members as potential risk factors. Reasonably, the infection is clustered in index cases' houses compared with neighbors' houses and this might be due to equal proximity to vector breeding sites or likely behaviors of family members with the index cases. As family size increases, there might be individuals who didn't have a chance to use bed nets, as universal coverage of mosquito nets is low in the country in general and the study area in particular.Regarding factors associated with asymptomatic malaria infection, previous malaria history increases 4.0 times the odds of having Ethiopia , 21, 26.


The onset of IgA nephritis in childhood and adolescence often develops into chronic glomerulonephritis with declining renal function. Although these long-term consequences are known, there is still a lack of evidence-based treatment recommendations in this age group. We report data from 22 pediatric patients who were biopsied to confirm the diagnosis of IgAN at our clinical center. 14 of them were treated with corticosteroids according to the recommendations for IgA nephritis vasculitis of the German Society of Pediatric Nephrology (GPN). Improvement was achieved in the majority of all cases, with a significant reduction in proteinuria five months after initiation of therapy. Our data suggest that treatment regimens for acute IgA nephritis and IgA vasculitis nephritis may be unified and are discussed in the context of current studies. IgA nephritis (IgAN) comprises a spectrum of heterogeneous courses, ranging from rapidly resolving glomerulonephritis to progressive loss of renal function . Onset iWhile mild manifestations of IgAN allow watchful waiting combined with renoprotective therapy, the pediatric nephrologist faces a difficult decision in more aggressive cases, as no evidence-based guidelines have been formulated to date. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of renin-angiotensin system blockade in children with proteinuria > 0.2 g/g creatinine. Despite widespread use of immunosuppressive therapy, especially glucocorticoids, there is no international consensus on their indication in more severe cases as strong trial-based evidence is still missing ,6.The aim of this small retrospective study and literature review is to highlight the challenges of pediatric IgAN in clinical practice and to discuss them in the context of current studies.We retrospectively reviewed the charts of 22 children who were diagnosed with IgAN after renal biopsy in our pediatric nephrology center from 2001 to 2021.Clinical findings such as hematuria and hypertension were assessed. Microhematuria was defined as microscopic evidence of more than 5 erythrocytes in a high-power field; macrohematuria meant a visible change of urine color. Hypertension was defined as a systolic and/or diastolic blood pressure above the 95th percentile according to age, height, and gender following the KiGGS-study . ProteinThe biopsy specimens were analyzed by a pathologist according to the Oxford classification (MEST score). For 14 biopsies preceding the updated 2017 classification , the C-sFollow-ups were carried out at four points in time: after 4 (2–6) weeks, 5 (3–7) months, one year (11–18 months), and two to three years (20–38 months). For patients with an observation period of more than 3.5 years, final follow-up data were also added (mean 5.8 years). Due to missing data points, the size of the patient collective varies as indicated. One patient with end-stage renal disease at initial presentation received kidney transplantation; all posttransplant clinical parameters were excluded from the study.2. Glucocorticoid therapy was restricted to 8 weeks and then replaced by alternative immunosuppression where necessary to reduce steroid toxicity. The side effects of steroid therapy were monitored by regular determinations of blood pressure, weight, and glucosuria in urine dipstick.Treatment modalities included renoprotection with angiotensin converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), immunosuppressive therapy , plasmapheresis, or hemodialysis, as well as kidney transplantation. The treatment followed the recommendations of the German Society for Pediatric Nephrology (GPN) for IgAVN  and aimep-values < 0.05 were considered statistically significant. Analyses were performed using SciPy for Python [Results were expressed as means with standard deviation and minimum–maximum values. Parameters such as proteinuria and eGFR over time were compared using the Wilcoxon signed-rank test, parameters of differently treated groups were compared by Mann–Whitney U test, and r Python . The stuWe studied 22 children and adolescents diagnosed with IgAN from 2001 to 2021 in the Department of Pediatrics, Adolescent Medicine and Neonatology, at the University Hospital of Freiburg, Germany. 2; 32% showed severely impaired renal function with an eGFR < 60 mL/min/1.73 m2, and in 41% proteinuria extended into the nephrotic range. All children were followed for a median of 3.5 years (2 months-10 years).Half of the children and adolescents initially presented with hypertension; 32% showed microhematuria and 68% macrohematuria. The mean proteinuria at biopsy was 3.2 ± 3.7 g/g creatinine and average eGFR 81.3 ± 49.7 mL/min/1.73 mThe average number of glomeruli in the biopsy sample was 31.8 ± 24.1 (8–107) per biopsy. The Oxford classification  showed 6As described in 2 body surface area (max. 3 × 500 mg) every 48 h, followed by prednisone p.o. in descending doses . This is consistent with the treatment of IgA vasculitis nephritis (IgAVN) patients, as recommended by the German Society of Pediatric Nephrology (GPN) in 2013. In patients with deteriorating eGFR despite intensified immunosuppression (corticosteroid therapy and cyclophosphamide), plasmapheresis is used as rescue therapy [Steroid therapy involved three intravenous administrations of methylprednisolone  at a dose of 300 mg/m therapy .2).Although treatment decisions were made on a case-by-case basis, the most important factors to initiate a steroid therapy were the evidence of crescents in the biopsy specimen (86% in the treated vs. 13% in non-treated group), nephrotic range proteinuria (57% vs. 13%), or severely impaired renal function (43% vs. 13% with an eGFR < 60 mL/min/1.73 mThe collected data (proteinuria and eGFR) of five follow up visits are shown in p < 0.001) from 3.2 ± 3.7 (0.29–12.5) to 0.5 ± 0.6 (0.08–2.1) g/g creatinine. However, the improvement in eGFR from 81.3 ± 49.7 (8.9–229.4) to 92.7 ± 32.4 (8.4–162.8) mL/min/1.73 m2 was not significant.Five months after start of therapy, protein excretion decreased significantly (p < 0.001) from 4.0 ± 3.4 (0.29–12.5) to 0.4 ± 0.5 (0.08–1.7) g/g creatinine after 5 months of follow-up. This subgroup is shown as light blue boxplots in Considering only the patients who received i.v. steroid therapy after diagnosis, there was also a significant reduction in proteinuria (2) was present in 50% (10/20). At later follow-up time points, patient numbers declined, but the percentages of proteinuria and impaired GFR did not change substantially.As shown in 2, p < 0.05 in Mann–Whitney U test). However, this study has limitations such as the small number of patients, the limited follow-up time, and the loss of some patients during this period. Therefore, it is primarily suitable for representing the short-term response to therapy.Treatment of newly diagnosed IgAN according to the GPN regimen for IgA vasculitis nephritis achieved an improvement in the majority of cases, with a significant reduction in proteinuria 5 months after initiation of therapy. Nonetheless, complete remission was only achieved in 25% of all cases, and additional immunosuppressants were used in six cases (27%). Interestingly, despite worse baseline conditions, eGFR tended to be better in the corticosteroid-treated patient group than in the untreated group during follow-up. After one year, mean eGFR was even significantly better in the treated group (118.6 vs. 86.5 mL/min/1.73 mIn the clinical setting, it is difficult to use immunosuppressive therapy with known side effects and unclear efficacy if the long-term renal damage is not foreseeable, especially because guidelines are based on insufficient evidence. Therefore, based on the existing literature on IgAN in childhood, we would like to discuss why, whom, and how to treat.Spontaneous remissions of mild IgAN have been described  and led In order to identify IgAN patients with poor prognosis already at initial diagnosis, many investigations have been conducted to evaluate corresponding risk factors. Early clinical or pathologic features that bear prognostic significance are summarized in International IgAN Prediction Tool at biopsy for adults, a version adapted to children and adolescents was developed in 2020 that promises to accurately predict the risk of a 30% decrease in GFR or ESRD [Based on the  or ESRD . The criThe question of how IgAN should be treated is the most controversial. Renoprotective therapy with ACEI or ARB is the basis of any treatment because of its positive effects, not only on hypertension but also on proteinuria and reduction of GFR decline . Its ben2 [However, the use of renin-angiotensin system blocking drugs alone does not always show sufficient response. A recent large study in China provides evidence of the benefit from additional immunosuppressive therapy for children with proteinuria ≥ 1 g/day and initial eGFR of >50 mL/min/1.73 m2 . The Eur2 . Steroid2 .Other immunosuppressive regimens involve cyclophosphamide , azathioIn summary, the available published experience suggests that early immunosuppressive therapy might have a beneficial effect on the long-term course of IgAN, at least in severe cases, but sufficiently large studies proving this assumption are outstanding. Our data showing improvement of proteinuria and stabilization of eGFR with an IgAVN treatment protocol and the very similar clinical and histological presentation of acute pediatric IgAN and IgAVN ,39 may j


Purpose: To explore the incidence, pathogens, treatment, and prognosis of endophthalmitis.Methods: Patients who were diagnosed with endophthalmitis from January 1990 to October 2020 at Peking Union Medical College Hospital were retrospectively reviewed and examined. Subgroup analysis was conducted regarding different initial treatment methods for eyes without concurrent retinal detachment (RD) at presentation.Results: A total of 249 eyes of 233 patients were included in this retrospective study. The most common clinical scenario was exogenous endophthalmitis (60.6%). The most frequent bacteria and fungi were coagulase-negative staphylococci (10.0%) and candida (6.8%), respectively. Retinal with/without choroid detachment was the most common complication after treatment. Patients with endogenous endophthalmitis were more likely to have binocular involvement; there were also more patients with diabetes mellitus or immunosuppressive diseases, and the prognosis of visual acuity (VA) was poorer. There were more eyes with concurrent RD at presentation that underwent serious complications after treatment (p < 0.05), and the visual outcome was worse than that without concurrent RD (p < 0.05). Subgroup analysis was conducted according to different initial treatments in eyes without concurrent RD. Group 1 received pars plana vitrectomy (PPV) with intravitreal injection of antibiotics (IVI) as initial treatment, Group 2 was initially treated with IVI only, and Group 3 was initially treated with nonsurgical treatment. More eyes that initially received IVI alone and nonsurgical treatment required additional treatments, especially additional PPV. VA in both Groups 1 and 2 significantly improved by the final VA. However, there was no significant difference in final VA between the two groups. There was an insignificant trend that serious posttreatment complications were more common in Group 1. In Group 1, 17 eyes received silicone oil or gas tamponade at the same time, whereas 62 did not. Eyes that were initially treated with PPV + IVI while without tamponade needed more additional treatments and additional IVI.Conclusion: Endophthalmitis is a devastating intraocular disease and requires early intervention. Endogenous endophthalmitis has a poorer visual prognosis than exogenous entity. PPV + IVI as an initial treatment may reduce additional therapy. Endophthalmitis, which often refers to bacterial or fungal infection of the vitreous and/or aqueous, is one of the most devastating intraocular diseases and usually causes irreversible visual impairment. It can be endogenous, caused by hematogenous bacteriaemia and/or fungaemic spreading to the eye, or exogenous, arising after trauma or eye surgery . In the The treatment of endophthalmitis, especially at the time of vitrectomy, is always under discussion. More than 20 years ago, the Endophthalmitis Vitrectomy Study (EVS) compared the efficacy of the vitrectomy group with the inject-only group and concluded that vitrectomy was beneficial only for eyes with light perception (LP) or worse than LP . With thThe purpose of our study was to explore the incidence, pathogens, treatment, and prognosis of endophthalmitis. The clinical characteristics of endophthalmitis with/without concurrent RD at presentation were evaluated and the prognosis of different initial treatment methods for eyes without concurrent RD was discussed, to provide a reference for ophthalmologists.This was a single-center retrospective study. We reviewed all patients with endophthalmitis admitted to Peking Union Medical College Hospital from January 1990 to October 2020 and recorded the demographic characteristics, general and ocular history, clinical settings, microbiological results, initial treatment, additional treatments, initial and final best-corrected visual acuity (BCVA), and serious complications after treatment. This study adhered to the Declaration of Helsinki of the World Medical Association and was approved by the Institutional Review Board/Ethics Committee of Peking Union Medical College Hospital. Written informed consent was provided to each patient before the surgery. The clinical diagnosis of endophthalmitis was determined using clinical signs and symptoms, including eye pain, the loss of vision, eyelid edema, conjunctival congestion and chemosis, anterior chamber inflammation , vitritis, decreased red reflex, and vitreous opacity in B-scan ultrasound . Treatmet-test, a paired t-test, or a nonparametric test . The chi-square test or Fisher’s exact test was used to analyze categorical variables. Multivariate logistic regression analysis was used to identify factors associated with poor visual prognosis. SPSS 26.0  was used for statistical analysis; p < 0.05 was considered statistically significant.All data were collected and evaluated by two retinal specialists (W.-F.Z. and X.-Y.Z.). The mean ± SD was used to evaluate continuous variables. Counts and percentages were used to categorize variables. Continuous variables were analyzed using an independent A total of 261 patients (277 eyes) were recorded with endophthalmitis. Enucleation or enucleation was performed in 28 eyes of 28 patients at presentation. At last, 249 eyes of 233 patients were included in this study .n = 14), chronic systemic chemotherapeutic agents (n = 1), and allogeneic hemopoietic stem cell transplantation (n = 1). There were 22 (8.8%) eyes with an ocular history of glaucoma, 11 (4.4%) eyes with retinal vein occlusion, 7 (2.8%) with proliferative diabetic retinopathy, 4 (1.6%) with age-related macular degeneration, 4 (1.6%) with idiopathic choroidal neovascularization, 1 (0.4%) with corneal endothelial decompensation, 1 (0.4%) with thyroid eye disease, and 1 (0.4%) with coloboma of choroid and iris on binoculars. There were 99 (39.8%) eyes with concurrent RD at presentation, whereas 150 (60.2%) eyes did not.This study included 140 males and 93 females. The average age of these patients was 47.20 ± 20.48 years . There were 108 (46.4%) patients who had only the right eyes affected, 109 (46.8%) who had only the left eyes affected, and 16 (6.9%) who had both eyes affected; 46 (19.7%) patients had a history of diabetes mellitus (DM), and 50 (21.5%) had a history of hypertension; 16 (6.9%) patients were immunocompromised due to chronic systemic corticosteroids , among which endophthalmitis after perforating injuries  was more common. Endogenous endophthalmitis accounted for 39.4%, and 16 patients were bilateral involvement.n = 25, 10.0%), followed by streptococcus  and Staphylococcus aureus . The most frequent fungus was candida . Detailed pathogens results were shown in Culture-positive pathogens were found in 96 (38.6%) of 249 eyes. The pathogens were divided into gram-positive cocci in 42 eyes (16.9%), fungus in 32 (12.9%) eyes, gram-negative bacilli in 14 eyes (5.6%), gram-positive bacilli in 8 patients (3.2%). Among gram-positive cocci, the most frequent pathogen was coagulase-negative staphylococci (99 (39.8%) eyes developed serious complications after treatment, including 53 (21.3%) eyes with retinal with/without choroid detachment, 20 (8.0%) eyes requiring evisceration or enucleation, 23 (9.2%) eyes with decreased VA to NLP, and 3 (1.2%) eyes with corneal decompensation. The mean time of follow-up was 326.18 ± 684.66 days .p < 0.05), accounting for 29.3 and 18.3%, respectively. There was no significant difference in initial VA and RD at the initial presentation. The intervention of eyes was significantly delayed in endogenous endophthalmitis. For initial treatments, approximately 35% of eyes accepted IVI as the initial treatment in both two groups. However, more eyes (27.6%) with endogenous endophthalmitis received the nonsurgical intervention as the initial treatment when compared with the exogenous group. More than 60% of eyes needed additional treatments (61.2 and 72.8%), and approximately 40% of eyes underwent serious complications after treatment (36.7 and 41.7%). Decreased VA to NLP was more common in endogenous endophthalmitis, whereas RD was more common in exogenous endophthalmitis. There were significant differences in the distribution of pathogens between the two groups (p < 0.05). Exogenous endophthalmitis had a significantly better VA prognosis than endogenous endophthalmitis (p < 0.05), and final VA was significantly improved than initial VA (p < 0.001). On the other hand, there was no significant improvement after treatment for endogenous endophthalmitis (p = 0.281).As shown in p < 0.05).The study eyes were divided into two subgroups according to whether there was concurrent RD at presentation. The clinical data were listed in p < 0.05). For “with RD Group,” more eyes developed retinal with/without choroid detachment (27.3 vs. 17.3%) and decreased VA to NLP (16.2 vs. 4.7%). There were also differences in the distribution of pathogens between the two groups (p < 0.05). More pathogens of eyes without concurrent RD were bacterial (31.3 vs. 17.2%). After treatment, the final VA of eyes without RD was significantly improved from logMAR 2.20 ± 0.61 to logMAR 1.72 ± 0.96 (p < 0.05). However, the final VA in eyes with RD was not improved when compared with the initial values (logMAR 2.27 ± 0.61 vs. logMAR 2.34 ± 0.65).The number of eyes with serious complications after treatment in “with RD Group” was significantly more than that in “without RD group” (p = 0.001) and serious complications after treatment  as the factors associated with final VA (p < 0.05) (Supplement).Binary logistic regression was used to identify factors associated with final VA improvement or not, including the presence of DM, hypertension, immunosuppression, initial VA, clinical settings, pathogens, days between symptoms and operation, with/without concurrent RD at presentation, and serious complications after treatment. The results showed concurrent RD . The proportion of bacterial infection in Group 1 and 2 was significantly higher than that in Group 3 for eyes with positive culture results , whereas fungi infection was more frequent in Group 3 (p < 0.05)  were significantly longer than in the other two groups. Endogenous endophthalmitis was more common in Group 3, whereas in the other two groups, posttraumatic and postoperative endophthalmitis was predominant ( < 0.05) .p < 0.05). In Group 3, 9 patients (11 eyes) refused the further operation suggested by individual ophthalmologists. There was no difference in the number of total additional treatments and the number of additional IVI for the three groups. However, the number of additional PPV was significantly more for the initial treatment with IVI and nonsurgical treatment (p < 0.05) (p < 0.05), logMAR 2.20 ± 0.69 to logMAR 1.84 ± 0.97 (p < 0.05), and logMAR 1.98 ± 0.67 to logMAR 1.49 ± 0.98 (p > 0.05), in Groups 1, 2, and 3 respectively. There were no significant differences in final logMAR BCVA among the three groups after treatment.Out of 62 eyes who were initially treated with PPV + IVI, 40 (64.5%) eyes underwent additional treatments. By contrast, among eyes that received IVI as initial treatment, there were 86.3% (44 out of 51 eyes) required additional treatments, especially PPV, which were significantly different ( < 0.05) . Althougp < 0.05). p < 0.05). VA improved from logMAR 2.28 ± 0.49 to logMAR 1.66 ± 0.90 (p < 0.05), logMAR 2.46 ± 0.30 to logMAR 2.08 ± 0.90 (p < 0.05) in eyes without tamponade group and with tamponade group, respectively. There were no significant differences in severe complications and final BCVA between the two ways.Of the 62 eyes initially treated with PPV + IVI, 17 eyes received silicone oil/gas tamponade at the same time, whereas 45 eyes did not. There was no difference in gender, age, presence of DM, HTN, and initial VA between the two groups. There are 41.2% (7 out of 17 eyes) and 73.3% (33 out of 45 eyes) requiring additional treatments  was avoided to prevent RD. Even so, 13% of patients who received a needle biopsy received additional treatment, compared to 8% who received a PPV as their initial treatment. At the same time, EVS found a 260% higher incidence of RD in the nonsurgical group than in the vitrectomy group, which proved that the infection itself was more devastating . In our Outcomes such as VA and RD rates after treatment were important in assessing the benefit of early PPV. It should be noted that in our study, final VA was significantly improved in both Groups 1 and 2 compared with that before treatment. However, the final VA between the two groups was not statistically different. A multicenter study on acute postprocedure endophthalmitis of 204 eyes conducted by Soliman MK et al. evaluated the visual outcome with IVI alone and IVI + early PPV within 1 week of presentation (86.6% of patients underwent PPV on the day of diagnosis). Their results showed no difference in final VA between the two groups, and early PPV could not predict good visual outcomes . Other sVitro experiments had shown that silicone oil can reduce the proliferation of bacteria. In addition, silicone oil was highly hydrophobic and had high interfacial tension, which could limit the movement of pathogens and reduce their conductivity. Vitrectomy with silicone oil had the tamponade effect on the retina and could reduce the incidence of RD . In a raSome limitations still existed. This was a retrospective study, and some bias in treatment selection cannot be ignored. Further prospective and randomized studies may be needed to address treatment selection in more detail. Second, different surgeons may affect surgical outcomes. In addition, various duration of follow-up may have an impact on the final vision.Endophthalmitis is a devastating intraocular disease and needs early intervention. Endogenous endophthalmitis has a poorer visual prognosis than exogenous entity. Eyes with concurrent RD at presentation usually underwent worse visual and anatomical outcomes. PPV + IVI as an initial treatment may reduce the number of additional therapies.


Objective: Gamma knife radiosurgery (GKRS) has served as an adjunctive treatment in Cushing’s disease (CD) for decades and has become a vital part of therapy in the management of CD. Biological effective dose (BED) is a radiobiological parameter with time correction, considering the cellular deoxyribonucleic acid repairment. We aimed to investigate the safety and efficacy of GKRS for CD and evaluate the association of BED and treatment outcome. Methods: A cohort study of 31 patients with CD received GKRS in West China Hospital between June 2010 and December 2021. Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test. Result: The mean age was 38.6 years old, and females accounted for 77.4%. GKRS was the initial treatment for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The mean endocrine follow-up duration was 22 months. The median marginal dose was 28.0 Gy, and the median BED was 221.5 Gy2.47. Fourteen patients (45.1%) experienced control of hypercortisolism in the absence of pharmacological treatment, and the median duration to remission was 20.0 months. The cumulative rates of endocrine remission at 1, 2, and 3 years after GKRS were 18.9%, 55.3%, and 72.21%, respectively. The total complication rate was 25.8%, and the mean duration from GKRS to hypopituitary was 17.5 months. The new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively. A high BED level (BED > 205 Gy2.47) was associated with better endocrine remission than a low BED level (BED ≤ 205 Gy2.47), while no significant differences were found between the BED level and hypopituitarism. Conclusions: GKRS was a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS. Cushing’s disease (CD) is caused by prolonged supraphysiological level of adrenocorticotropic hormone (ACTH) from pituitary adenoma or hyperplasia, resulting in hypersecretion of cortisol from adrenal glands, which is related to hypertension, diabetes mellitus, centripetal obesity, osteoporosis, mood disorders, and even shortened life span . The preThe biological effective dose (BED) is a radiobiological parameter with time correction that considers cellular deoxyribonucleic acid repair during radiosurgery ,8. The oData were collected from 31 patients with CD who had undergone GKRS in West China Hospital of Sichuan University during June 2010 and December 2021. The inclusion criteria for this retrospective study included diagnosis of Cushing’s disease as determined by an endocrinologist and neurosurgeon, and follow-up duration ≥ 6 months after GKRS with sufficient data. The exclusion criteria for the study consisted of endocrine follow-up< 6 months, other types of pituitary adenomas, and deficient data regarding outcomes. Institutional review board approval was obtained for this study (2022/958).The baseline data consisted of general conditions of the patients, tumor characteristics and GKRS parameters. General conditions of the patients included age, gender, coexisting disease, hormone levels of the pituitary-target organs prior to GKRS, and imaging data. Tumor characteristics included tumor volume and Knosp grade. The tumor volume was calculated as maximum height × maximum length × maximum width ×π/6. The GKRS parameters included marginal dose, maximum dose, isodose line, number of isocenters, and maximum point dose to the optic apparatus. Neuroimaging, biochemical tests, and complications were evaluated during the follow-up.Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test (1 mg DST). An increase in tumor volume ≥ 20% was defined as tumor progression, whereas a reduction in tumor volume ≥ 20% was defined as tumor regression, and the change between them was defined as stationary compared with pre-GKS volume.Twenty-six patients underwent the Leksell Gamma Knife (Elekta C) between June 2010 and December 2019, and five patients then received the Leksell Gamma Knife (Elekta ICON). First, a head frame was applied under local anesthesia. Second, thin slice (≤1 mm) MRI images were acquired with the frame in place. Then, the neurosurgeon and radiologist collaborated to establish the treatment plan. Generally, maximum doses to optic structures were kept to less than 9 Gy by optimized tumor treatment plans. Last, positioning the patient in the gamma knife, we delivered the plan after the head frame was rigidly affixed to the treatment table.2.47 [We calculated the BED via a simplified approach, which took into account the beam-on time, overall time, marginal dose, and isocenter, with an α/β ratio of Gy2.47 . For the2.47 .p value of <0.05 was defined as statistically significant.Statistical analyses were performed using SPSS version 23 . Descriptive statistics were performed for all available data. Kaplan-Meier and actuarial methods were used to perform time-dependent analyses for endocrine remission. A A total of 31 patients with CD received GKRS in this study . The med3 before GKRS. The median marginal dose was 28.0 Gy (range: 16–33 Gy), and the median coverage percentage was 96.7%. The median maximum dose received by the optic apparatus and pituitary stalk was 6.8 Gy (range: 1.8–9.1) and 11.8 Gy (range: 3.6–25.1), respectively. The mean beam-on time was 1.5 h (range: 0.5–2.6), and the median treatment dose rate was 1.8 Gy/m (range: 1.3–2.9). The median BED was 221.5 Gy2.47 (65.3–316.7).GKRS was the initial therapy for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The median endocrine follow-up duration and radiological duration were 22 months (range: 6–126) and 18 months (range: 8–127), respectively. The median tumor volume was 608.0 mm2.47 VS BED ≤ 205 Gy2.47). The actuarial rates of endocrine remission at 1 and 2 years after GKRS were 9.1% and 35.1%, respectively, in the low BED group (BED ≤ 205 Gy2.47); and 25.0% and 72.7%, respectively, in the high BED group (BED > 205 Gy2.47) (p = 0.041) as seen in 2.47) was associated with better endocrine remission than a low BED level (BED > 205 Gy2.47). There were 21 patients with complete imaging data. After GKRS, tumor control was achieved in 20 patients (95.2%), and the median tumor volume decreased from 608 mm3 to 115 mm3. However, 1 patient (4.8%) suffered tumor progression . The actuarial rates of the new hypopituitarism rate at 1, 2, and 5 years were 9.1%, 18.2%, and 45.5%, respectively, in the low BED group (BED ≤ 205 Gy2.47) and 4.1%, 35.2%, and 35.2%, respectively in the high BED group (BED > 205 Gy2.47) (p = 0.726) as seen in The total complication rate was 25.8%. Of the eight patients (25.8%) who developed a new hypopituitary after GKRS, six patients had hypothyroidism, and two patients had growth hormone deficiency. The actuarial rates of the new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively as seen in 2.47 was associated with higher endocrine remission rate without increasing the risk of hypopituitarism.The main purpose of the treatment of patients with CD was to relieve hypercortisolism, resect the tumor mass, and preserve normal pituitary function . RadiosuThere was no consensus in the definition of biochemical remission for CD patients . Several2.47) and low BED (BED > 228 Gy2.47) [2.47) was associated with better endocrine remission compared with a low BED level (BED ≤ 205 Gy2.47).Increasing evidence has shown that a high level of BED is a positive factor associated with endocrine remission. Anne et al. evaluated the BED in a series of 26 CD patients who underwent GKRS and defined the BED level as high BED (BED > 228 Gy Gy2.47) . They fo2.47 were associated with a 14-fold increase in the risk of hypopituitarism compared with the patients exposed to BED ≤ 45 Gy2.47 [2.47 as the cut-off point, and there was no significant difference between low BED and high BED. Although we applied the same methodology described by Jones and Hopewell, the results of BED exhibited discrepancies, as the minimum BED was 65.3 Gy2.47 in this study, which was significantly higher than that in the study by Graffeo et al. This suggests that the calculation method of BED needs further specification in detail.Hypopituitarism is a common radiation-associated adverse event for pituitary adenoma patients after GKRS. The hypopituitary rate ranged from 15.0 to 50.0% for CD after GKRS ,17,18,21Dose, dose rate, and any scheduled or unscheduled interruption of treatment determines the overall treatment duration, while the longer the overall treatment duration, the greater the chance of repair during exposure, which collectively alters the radiation biological effectiveness of the treatment. Voxel-by-voxel calculations can provide the real BED, rather than being based on whole-exposure volumes, with a daunting amount of calculation nevertheless. These estimation strategies must contain all kinds of assumptions which can lead to system errors. In practice, a balancing or trade-off, between accuracy and operability is often necessary . A numbeMany studies have reported that GKRS was preferred for the CD patients accompanying severe coexisting. Gupta et al. reported that 21 patients with CD underwent initial GKRS, and the biochemical remission rate reached 81% at 5 years. In this study, 21 patients received primary GKRS, and one-third of them achieved remission. However, a subset of CD patients with severe symptoms needed to correct hypercortisolemia and provide rapid symptom palliation, and the drawback of delayed onset efficacy in GKRS was displayed. In addition to transsphenoidal surgery, bilateral adrenalectomy (BLA) was a definitive treatment to relieve to hypercortisolemia for patients with severe symptoms. Bunevicius et al. retrospectively included 50 patients with CD who underwent SRS before BLA . The risAlthough we found positive results in this study, several certain limitations should be mentioned. First, we drew a conclusion based on a limited sample size, which can influence the reliability of the results. Second, we found a significant difference between BED and treatment outcome, but we did not exclude the interference of confounding factors due to the limitation of sample size and the relationship between BED and outcome should be studied further. In addition, although the methodology of estimated BED reported by Jones and Hopewell was applied for several studies, the BED in this study was the approximate values for the entire treatment volume, instead of voxel calculations of the actual treatment BED.2.47 was associated with higher remission rate without increasing the risk of hypopituitarism. Further study should be performed to standardize the methodology of BED in detail and investigate the relationship between BED and the outcome of GKRS.GKRS is a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS. BED > 205 Gy


Bipolar Disorder (BD) is a mental disorder characterized by long hospitalizations and frequent need for acute psychiatric care. Hospitalizations represent a valuable quality of care indicator in BD.The aim of this study was to describe a nationwide perspective of BD related hospitalizations and to use a BigData based approach in mental health research.We performed a retrospective observational study using a nationwide hospitalization database containing all hospitalizations registered in Portuguese public hospitals from 2008 to 2015. Hospitalizations with a primary diagnosis of BD were selected based on International Classification of Diseases version 9, Clinical Modification (ICD-9-CM) codes of diagnosis 296.xx .A total of 20,807 hospitalizations were registered belonging to 13,300 patients. 33.4% of the hospitalizations occurred in male patients and the median LoS was 16.0 days. Mean age was 47.9 years and male patients were younger. 59 hospitalizations had a deadly outcome (0.3%). The most common cause of hospitalization in BD was the diagnosis code 296.4x  manic) representing 34.3% of all hospitalizations, followed by the code 296.5x  depressed) with 21.4%. The mean hospitalization charges were 3,508.5€ per episode, with a total charge of 73M€ in the 8-year period of this study.This is a nationwide study using BigData analysis giving a broad perspective of BD hospitalization panorama at a nationwide level. We found differences in hospitalization characteristics by gender, age and primary diagnosis.No significant relationships.


There is limited understanding on the impact and burden of high PM2.5 concentrations on morbidity in these countries. In this study, we explore the association of PM2.5 and the risk of respiratory hospital admissions in Kuwait. A time-series regression model was used to investigate daily variations in respiratory admissions and PM2.5 concentrations from 2010 to 2018. Due to the lack of historical air quality sampling in Kuwait, we used estimated daily PM2.5 levels from a hybrid PM2.5 prediction model. Individual and cumulative lag effects of PM2.5 over a 5-day period were estimated using distributed lag linear models. Associations were stratified by sex, age, and nationality. There were 218,749 total respiratory admissions in Kuwait during the study period. Results indicate that for every 10 μg/m3 increase in PM2.5, a 1.61%  increase in respiratory admissions followed over a 5-day cumulative lag. Our estimates show that a 10 μg/m3 reduction in average exposure will potentially avert 391 yearly respiratory admissions , with 265 fewer admissions among Kuwaitis  and 262 fewer admissions among children under 15 years of age . Different strata of the Kuwaiti population are vulnerable to respiratory hospitalization with short-term exposure to PM2.5, especially those under 15 years of age. The findings are informative for public health authorities in Kuwait and other dust-prone countries.Dust is a major component of fine particulate matter (PM To a2.5 exposure by calculating the potential admissions averted for every 10 μg/m3 reduction. We used the approach presented by Dominici, et al.  = 35) and the median PM3 increase in PM2.5 exposure for same-day exposure up to 5 days after exposure. 3 increase in same-day PM2.5 exposure and a 1.61%  increase over a 5-day cumulative distributed lag. Moving average lagged effects for 3- and 5-days were significant, showing an increase in total admission of 1.32%  and 1.38% , respectively. Although the confidence intervals overlap, there was some heterogeneity in effect size across age groups with every 10 μg/m3 increase in exposure contributing to a 1.76%  increase in admissions among those under 15 years of age, and a 2.24%  increase in those above 65 years of age. The risk estimates were not statistically significant for the 15–64 age group. A significant association was observed in both males and females, with each 10 μg/m3 exposure increment contributing to 1.52%  and 1.72%  increase in admissions, respectively. Furthermore, Kuwaitis showed a higher risk of admission than non-Kuwaitis in total. Based on our in-depth subgroup analyses, stratifying the subpopulations by nationality, then by sex, then by age , we foun3 reduction in PM2.5 exposure in Kuwait. Our estimates show that a 10 μg/m3 reduction in average exposure may potentially reduce respiratory admissions by 391  patients each year. 2.5 over a historical period in Kuwait that otherwise did not exist. We used this dataset to investigate the associations with respiratory-related hospital admissions. We estimate that a total of 391 respiratory admissions each year can be averted if PM2.5 levels in the country drop by 10 μg/m3. Overall, for every 10 μg/m3 increase in PM2.5, there is a 1.61% increase in total respiratory admissions over a 5-day cumulative distributed lag. Different strata of the Kuwait population are vulnerable to PM2.5 exposure, especially the elderly and those under 15 years of age. In this study, we were able to leverage statistical models to obtain a spatiotemporally resolved PM2.5 impacts on the Kuwaiti population by age, sex, and nationality were investigated to determine the vulnerability of the population. Those aged 65 and over were especially susceptible to PM2.5 exposure, followed by those under 15 years of age. The strength of these associations is consistent with studies showing stronger impacts of PM2.5 on respiratory admissions among the elderly [2.5 exposure is likely contributing to larger effect estimates in the presence of these diseases [2.5 on respiratory outcomes for males and females in different counties in the USA found that PM2.5 exposure was associated with a higher relative increase in hospitalization for respiratory tract infections and asthma in women than in men [2.5 exposure. We found Kuwaiti females to have a high risk of admission compared to males. The exact reason for these differences is unclear, but could be attributed to physiological, behavioral, and/or psychosocial determinants of health [2.5 exposure affects the health of men and women differently needs to be further explored.Differences in PM elderly . Adverse elderly ,27,28. Idiseases ,30,31. Tdiseases . With ren in men ,33. Simin in men  reportedf health . Possiblf health . The pat2.5, which is more quantifiable and can provide better regulatory inference and allow for comparison across different studies. Our finding could be influenced by social factors related to access to healthcare, where Kuwaitis can utilize public hospital services for free, whereas non-Kuwaitis must pay a fee to be admitted and/or receive treatment. This likely played a role in potentially underestimating the risk of respiratory hospital admissions among the non-Kuwaiti subgroup. In Thalib and Al-Taiar’s [2.5 measures instead and provided an analysis on hospital admissions using recent data from the past decade.As expected, non-Kuwaiti males exhibited a large relative risk of admissions. Non-Kuwaiti adult males are more vulnerable to higher ambient pollutant exposure given the outdoor nature of many migrant worker jobs such as construction and sanitation . This is-Taiar’s  paper in3 rise in exposure PM2.5 at lag 0–2 days [2.5 and daily mortality and hospital admissions concluded that a 10 μg/m3 increment in PM2.5 is associated with an increase in risk of admission for respiratory diseases by 0.96% [Overall, our findings are in line with previous studies conducted globally. A study in China reported a respiratory admission relative risk of 1.06 per 10 μg/m0–2 days . A meta-2.5 and respiratory outcomes is of optimum importance. Particulate matter exposure impacts health negatively especially among individuals with pre-existing lung conditions. PM inhalation among respiratory patients is associated with pulmonary function decrements where reductions in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) are observed ,40,41,422.5 with respiratory admissions. However, the study has a few limitations. The use of estimated daily mean PM2.5 measurements rather than direct measurements from monitoring stations in Kuwait is potentially associated with exposure measurement error. However, these PM2.5 prediction models ensure that there are no days with missing data. Although we believe that the PM2.5 prediction models had good predictive ability (R2 = 0.71), it is still less preferred than direct ground monitoring readings, as less measurement error in the exposure would occur had we measured PM2.5 continuously from ground stations for the study period. Despite this, the predictions are the best available data, since historical ground monitoring in Kuwait does not exist. Additionally, in this study, we assumed that all individuals in the population were exposed to PM2.5 at the same level, since we did not have address data for admitted patients. Moreover, for future directions, it would be valuable to examine hospital readmissions to assess their association with exposure to PM2.5 in the long-term. Finally, the findings of this study should be interpreted within the local context and population characteristics in Kuwait. Based on the literature review, we believe that this is the first study in the region to examine the association of PM2.5 exposures on daily respiratory admissions in Kuwait. Our analysis suggests that different strata of the Kuwaiti population are vulnerable to respiratory disease hospitalization when exposed to PM2.5 in the short-term, especially the elderly and those under 15 years of age. The results of the study highlight the importance of preventative care for Kuwait’s susceptible population to decrease the risk of respiratory complications during bad weather events. Potential warning systems can be put in place with air quality alerts to protect those who are vulnerable, especially children. In addition, with such information, hospitals would be able to predict increases in admissions and, thus, be better equipped to handle high volumes of emergency visits during days with higher PM levels. These findings contribute to the limited evidence related to the association between health and exposure to dust-dominant ambient PM2.5 in Kuwait and in the Middle East. The present study is the first to explore the impact of PM