Objective: There is limited literature comparing the uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion outside-in approach (ETLIF (O)) with the inside-out approach (ETLIF (I)). Methods: Radiological evaluation was performed on disc height restoration and coronal wedging angle, and operation time  and clinical evaluation were made. Result: 48 cases of inside-out and 38 cases of outside-in cases were included. Compared to inside-out, the outside-in approach had significantly less operative time required to resect inferior articular process: 36.55 ± 10.37, and total operative time: 87.45 ± 20.14 min compared to 49.83 ± 23.97 and 102.56 ± 36.53 min, respectively, for the inside-out approach, p < 0.05. Compared to the preoperative state, both cohorts achieved significant improvement of VAS and ODI at post-operative 1 week, 3 months and at final follow up. Both cohorts achieved statistically significant increased disc height with 5.00 ± 2.87 mm, 5.49 ± 2.33 mm and statistically significant improvement in coronal wedge angle with 1.76 ± 1.63°, 3.24 ± 2.92° in the inside-out and outside-in approaches respectively. Conclusions: Complete removal of inferior articular process is the key part of endoscopic fusion with two methods that can be applied: an inside-out approach or an outside-in approach. Comparing both techniques, the outside-in approach has a shorter operative time required for inferior articular process resection and total length of operation with similar good clinical and radiological outcomes. With the evolution of endoscopic spine surgery, there are an increasing variety of endoscopic techniques being applied in lumbar spine surgery ,2. Both Informed consent was obtained from all patients that participated in this retrospective comparative study and was reviewed by Institutional review board of Nanoori Hospital, Seoul, Republic of Korea (NR-IRB 2021-004).The inclusion criteria were patients who presented with neurogenic claudication and back pain who had failed the minimum 6 weeks of conservative treatment and had one of the following diagnoses: (1) spinal stenosis with instability of lumbar segment; (2) grade 2 and below spondylolisthesis; (3) foraminal stenosis; or (4) Recurrent disc herniation. Each patient had a single level uniportal endoscopic posterolateral lumbar interbody fusion (ETLIF). The inferior articular process resections were carried out in two distinct approaches. In the uniportal endoscopic posterolateral lumbar interbody fusion using inside-out approach, ETLIF (I), the inferior articular process (IAP) was resected starting from the spinolaminar junction outwards towards the lateral laminofacet junction ,18,19. IWe excluded patients who had spinal fusion surgery due to revision spinal fusion surgery, trauma, tumor, pseduoarthrosis, infection, congenital spinal deformity, sagittal malalignment and coronal malalignment with more than 10 degrees coronal curve.Inferior articular process is a process of a cephalad vertebra of the spinal segment that lies on each side of the neural arch and projects downward and processes vertical convex articular facets which face anterolaterally articulating with the superior articular process of the next caudal vertebra. It is convex dorsally and laterally A 21]. I. I21]. IUniportal endoscopic posterolateral lumbar interbody fusion, ETLIF technique has been described ,18,19,200 viewing angle, 10 mm outer diameter, 6 mm working channel diameter and 125 mm working length endoscope to begin the surgical procedure.The patient was positioned prone on a Wilson Frame on top of a radiolucent operating table with the spine in slight flexion under general anesthesia. The Wilson Frame was flattened during pedicle screws and rod insertion for reduction maneuvers. We performed facet resection and cage insertion from the patient’s symptomatic side. Cage insertion was done before pedicle screws insertion in all cases. We used a 1.6 cm skin incision on the cephalad vertebral pedicle of the symptomatic side and level for facet resection, disc preparation and cage insertion. A wider 3 cm fascia incision was made for more mobility of the endoscope. Serial dilation with guidewire, obturators and finally a working retractor cannula was docked on the medial part of the inferior border of IAP. After docking to the safe area, we moved the endoscope to Wu’s point or Kim’s point of the cephalad vertebra for ETLIF (I) and ETLIF (O), respectively . We usedWe used normal saline with an irrigation pressure of 25–40 mm Hg with an irrigation pump during most parts of the endoscopic fusion procedure. We first performed soft tissue dissection around the medial aspect of the facet joint, the medial edge of laminar and isthmus with radiofrequency ablator. We looked for the endoscopic landmark of the spinolaminar junction and medial rounded edge of the facet joint A,AI. We In ETLIF (O), the abovementioned steps for handling of IAP were done in the reverse manner. Endoscopic soft tissue dissection of multifidus was done with focus on the lateral aspect of the facet joint A,AI. In We followed resection of inferior articular process which was isolated within the retractor tube and removed as an autograft A. SuperiThe open beveled working cannula of 13.7 mm outer diameter and 10.2 mm inner diameter and placed on the disc while pointing the open bevel away from the exiting and traversing nerves to protect the neural elements. Gentle retraction of the neural elements could be completed with the retractor tube. Radiofrequency ablator and a blunt probe was used to perform annulotomy. Disc preparation and denudation of the end plate cartilage was carried out with an endoscopic drill and blunt bent probe until punctate bleeding of the subchondral bone, and the disc was retrieved with forceps E. Upon sThe Wilson frame was subsequently flattened after cage insertion, and percutaneous pedicle screws were inserted under fluoroscopic guidance in standard fashions with or without cement augmentation. We introduced two bent rods of appropriate length and lordosis through the percutaneous rod. We performed compression and final tightening of the set screws and closed the wound in layers.Both cohorts of patients underwent single level ETLIF performed in the period of October 2018 to August 2020 by a senior surgeon. Both techniques were started in October 2018.We collected and analyzed baseline demographics data, operative data of inferior articular process resection time and total operative time, preoperative and postoperative radiographic roentgenogram data in disc height and coronal wedge angle . We meast-test was used for comparison of pre-operative and post-operative radiological roentgenogram results on disc height and coronal wedge angle. Clinical visual analogue scale (VAS) and Oswestry Disability Index (ODI) were measured at pre-operative, 4 weeks post-operative, 3 months post-operative and final follow up as well as MacNab’s score at final follow up reported by the patients were analyzed with paired t test. A value of (p < 0.05) was considered significant within each group of data. Independent T test was used to compare the clinical data of VAS and ODI and radiological roentgenogram results on disc height and coronal wedge angle.Clinical data was analyzed with SPSS version 18 statistical analysis software . The continuous variables were expressed as mean and standard deviation (SD). The paired p < 0.05.From the period of October 2018 to August 2020, a total of 86 single levels ETLIF were performed in patients who met the inclusion and exclusion criteria, of which 48 were ETLIF (I) and 38 were ETLIF (O). No statistical difference in mean age of 65.02 ± 9.69 years in ETLIF (I) and 68.39 ± 11.41 years in ETLIF (O). The mean follow up was 14.73 ± 5.33 months in ETLIF (I) and 11.58 ± 3.81 months in ETLIF (O), In terms of the lumbar level treated in ETLIF (I), two L2/3, four L3/4, thirty-five L4/5 and seven L5/S1 ETLIF (I) were treated. All patients underwent general anesthesia for surgery. Four levels were fused for spinal stenosis with instability, forty levels were fused for spondylolisthesis and four levels were fused for foraminal stenosis.In terms of lumbar level treated in ETLIF (O), there were five L2/3, two L3/4, twenty- two L4/5 and nine L5/S1 ETLIF (O) treated. All patients underwent general anesthesia for surgery. Five levels were fused for spinal stenosis with instability, thirty levels were fused for spondylolisthesis, two levels were fused for foraminal stenosis and one level was fused for recurrent disc herniation. There was no statistical difference between the two cohorts in terms of levels of operation and indication of operation .p < 0.05 (ETLIF (O) achieved a statistically shorter time for inferior articular process resection and total operation time of 36.55 ± 10.37 min and 87.45 ± 20.14 min, respectively, as compared to ETLIF (I) of 49.83 ± 23.97 min and 102.56 ± 36.53 min respectively, p < 0.05 .p < 0.05. ETLIF (O) achieved statistically significant improvement of disc height and coronal wedge angle with 5.49 ± 2.33 mm and 2.87 ± 2.25°, p < 0.05. Between the ETLIF (I) and ETLIF (O) cohort, both achieved comparable improvement of disc height and coronal wedge angle with no statistical difference. There was no implant malposition or loosening in both cohorts of patients (ETLIF (I) achieved a statistically significant improvement of disc height and coronal wedge angle with 5.00 ± 2.87 mm and 1.76 ± 1.63°, patients .In terms of complications for ETLIF (I), we had two complications (4%) with one retained drain tip which was removed under local anesthesia and one revision ETLIF (I) for adjacent segment disease of L3/4 one year after ETLIF (I) of L4/5 performed. Both had good McNab’s criteria outcome and had improvement of his preoperative symptoms without neurological sequelae. In terms of complications for ETLIF (O), we had one complication (2.6%) for an adjacent disease of L3/4 with prolapsed intervertebral disc one year after ETLIF (O) of L2/3, he was treated with transforaminal endoscopic lumbar discectomy and had done well postoperatively with good McNab’s criteria outcome and improvement of his preoperative symptoms without neurological sequelae. There were no neurological complications in both the ETLIF groups of patients.p < 0.05. The preoperative, 1 week post-operative, 3 months post-operative and final follow up Oswestry Disability Index (ODI) had the mean and range of 74.38 ± 8.72, 33.50 ± 6.52, 26.25 ± 4.72 and 23.81 ± 4.85 respectively. Compared to the preoperative state, there was statistically significant improvement in ODI score at 1 weeks, 3 months and final follow up: 40.88 ± 11.23, 48.13 ± 10.86 and 50.56 ± 10.63, p < 0.05. In terms of MacNab’s criteria, 1 had fair, 26 had good and 21 patients had excellent scores with 97.9% good to excellent score  preoperative, 1 week post-operative, 3 months post-operative and final follow up, the Visual Analog Scale (VAS) score had the mean and standard deviation of 7.65 ± 1.25, 3.44 ± 0.85, 2.33 ± 0.88 and 1.83 ± 0.86, respectively. Compared to the preoperative state, there was statistically significant improvement in VAS score at 1 weeks, 3 months and final follow up: 4.21 ± 1.49, 5.31 ± 1.68 and 5.81 ± 1.61, nt score .p < 0.05. The preoperative, 1 week post-operative, 3 months post-operative and final follow up Oswestry Disability Index (ODI) had the mean and range of 73.21 ± 10.62, 32.63 ± 5.44, 27.16 ± 5.31 and 25.05 ± 5.52, respectively. Compared to the preoperative state, there was statistically significant improvement in ODI score at 1 weeks, 3 months and final follow up, 40.58 ± 10.17, 46.05 ± 10.80 and 48.16 ± 11.71, p < 0.05. In terms of MacNab’s criteria, 1 had fair, 27 had good and 10 patients had excellent scores with 97.4% good to excellent score  preoperative, the 1 week post-operative, 3 months post-operative and final follow up Visual Analog Scale (VAS) score had the mean and standard deviation of 7.58 ± 1.31, 3.26 ± 0.64, 2.39 ± 0.82 and 2.16 ± 0.86 respectively. Compared to the preoperative state, there was statistically significant improvement in VAS score at 1 weeks, 3 months and final follow up: 4.32 ± 1.32, 5.18 ± 1.47 and 5.42 ± 1.48, nt score .Comparing the clinical results of ETLIF (I) and ETLIF (O), there was no statistically significant difference in terms of VAS, ODI and change in disc height and change of coronal wedge angle. There was no statistically significant difference between the two cohorts in terms of percentage of McNab’s score in good and excellent outcomes .The proposed benefits of lumbar endoscopic spine surgery in the treatment of degenerative spine conditions were similar to other minimally invasive procedures ,22. StudSuch benefits lead to an increasing trend in the number of endoscopic spine procedures performed and a corresponding increased volume of publications on endoscopic decompression and KLIF type of endoscopic fusion; there was paucity of literature in ETLIF ,19,22,25The main difference between KLIF ,26 and EThe attraction of putting a large interbody cage with less soft tissue damage and yet providing direct decompression of neural elements led to the development of ETLIF ,18,19,20Clear identification of the start and end point of the endoscopic drilling can promote efficiency in operating time, limit unnecessary soft tissue bleeding and time spent for hemostasis and, most importantly, avoid neural injuries. The ETLIF (O) technique allows early and precise identification under endoscopic vision of most cephalad lateral aspect of inferior articular process intersection with superior articular process (Kim’s point) and subsequent endoscopic drilling in oblique outside-in direction towards the Wu’s point. In ETLIF (I) dissection of multifidus and rotatores spinae in the early part of the surgery is necessary to identify the midpoint of the arc of lamina from the spinolaminar junction and most inferior medial aspect of inferior articular facet (Wu’s point) and endoscopic drilling starts from Wu’s point in the oblique inside-out direction towards Kim’s point. We found that in our cohort of patients, ETLIF (O) achieved statistically significant reduction in operation time for inferior articular process resection and overall total operation time. ETLIF (O) spent a mean 36.55 ± 10.37 min (73.3%) for inferior articular process resection time, 87.45 ± 20.14 min (85.2%) for total operation time required by ETLIF (I), 49.83 ± 23.97 min for inferior articular process resection time and 102.56 ± 36.53 min for total operation time, respectively. We felt that by doing ETLIF (O), we spent less time handling soft tissue dissection and hemostasis of the rotatores spinae muscle which are located medial to Wu’s point. As there is limited muscle mass lateral to the Kim’s point, we could decrease time spent in the early part of surgery dissecting soft tissue as compared to starting at Wu’s point. Being able to identify these key endoscopic anatomical landmarks allowed surgeons to be oriented early in the fusion surgery and decisively start endoscopic drilling of isthmus from outside in direction, which saved time in surgery.Care must be taken in dissection of both start points. Lateral to Kim’s point in the superficial layer is the superior articular artery which can be controlled by radiofrequency ablation. However, the radicular artery is lying ventral to the intertransverese membrane deep in Kim’s point, and inadvertent damage can lead to significant bleeding and obstruction to endoscopic visualization, sometimes even requiring conversion to microscopic surgery in literature . Medial As the subsequent steps in handling of superior articular process, end plate and cage insertion were similar in both ETLIF (I) and ETLIF (O): they both allowed a large cage to be inserted in the intervertebral space. We found both ETLIF approaches to be as proficient in correction of coronal wedge angle, disc height, improving clinical parameters of VAS pain score and ODI score with statistical improvement within each cohort compared to pre and postoperative parameters but no statistical difference was found between the two cohorts. These findings are concordant with earlier studies and meta-analysis ,19.Recent metanalysis of endoscopic fusion showed ODI significantly improved by twice as much as the MCID and the VAS for back and leg pain showed significant improvements over the MCID. The perioperative complications were usually minor . We founDespite differences in the handling of IAP, the ETLIF (O) and ETLIF (I) techniques both still have significant technical difficulties in adequate end plate preparation and cage insertion. The limited size of the working channel (6 mm) in uniportal endoscope requires the use of a relatively small endoscopic drill and instruments for disc preparation as compared to open or biportal surgery. The challenge is to ensure endoscopic drilling does not violate the end plate. The clarity of endoscopic vision within the intervertebral disc space can help to decrease the risk of inadvertent damage to the end plate. Fluoroscopic guided cage insertion with subsequent endoscope inspection requires firm handling and an understanding of the position of the retractor tube in relation to the neural element. Both of these technical difficulties have a steep learning curve. We hoped that by highlighting the anatomical landmarks and suggestion of these two ways of approaching the IAP in ETLIF (O) and ETLIF (I), we could help to shorten the learning curve at the first stages of ETLIF.There was a steep learning curve with higher possible complication rates in the early phase of practice . We founThere are several differences and possible confounding factors in this study: the data was obtained as a retrospective comparative cohort study with patients who had undergone ETLIF (O) and ETLIF (I). There could be inherent selection and performance bias in the study. Pre-operative data such as comorbidities, Charlson Morrison Index, BMI and smoking history were not collected which might introduce confounders in the study. We limited these confounding factors by having the same team of anesthetists and surgeons for both cohorts of operations performed in the data set for both groups. There was a statistically significant different, though not clinically significant, follow up period between the two cohorts due to medium term duration follow up. We continued to follow up on these patients with a view to showing the effect of a longer follow up in the future to evaluate the clinical and radiological data in the long term. Fusion and subsidence evaluation was not performed as this IRB approval did not include the CT scan in our evaluation. A prospective randomized controlled study would be more ideal to eliminate these bias.In endoscopic posterolateral transforaminal lumbar interbody fusion, complete removal of Inferior Articular Process is the key part of surgery with two methods that can be applied: an inside-out approach or an outside-in approach. Comparing both techniques, the outside-in approach has a shorter operative time required for inferior articular process resection and a shorter total length of operation with similar good clinical and radiological outcomes.


Our objective was to determine current practice in Switzerland regarding the use of pNPWT in abdominal surgery. An online survey was carried out to evaluate the use of pNPWT among abdominal surgeons in Switzerland. One hundred and ten participants replied to the survey from 16.12.2019 to 15.01.2020. Eleven were excluded, leaving 99 responders for analysis. Seventy participants (70.7%) were using pNPWT, 3 (3%) have stopped using it and 26 (26.3%) have never used it. pNPWT was used on midline laparotomy by 63 responders (90%), closed stoma wounds by 21 (30%), closed perineal wounds by 20 (28.6%), Pfannenstiel incisions by 18 (23.7%), groin incisions by 16 (22.9%), subcostal incisions by 13 (18.6%), Mc Burney incisions by 3 (4.3%) and other incisions by 18 (25.7%). Forty-eight participants (68.6%) used pNPWT on less than 10% of patients, 14 (20%) on 10–25% of patients, six (8.6%) on 25–50% of patients and two (2.9%) on 75–100% of patients. Suggestions for improvement to pNPWT were: better sealing, recyclable system, better adaptation to the perineum, smaller device, reduced cost and possibility to check the surgical wound through the dressing. In conclusion, pNPWT is widely used among Swiss surgeons, mostly on midline incisions. However, most of them apply pNPWT on a small proportion of patients only. Suggestions for improvement were a better sealing for complex wounds, reduced cost and possibility to check the wound during the therapy.The online version contains supplementary material available at 10.1007/s13304-021-01017-3. Prophylactic negative-pressure therapy (pNPWT) consists of an aspirative plaster connected to a pump applying negative pressure on a closed surgical wound. In this regards, pNPWT differs from the usual negative-pressure wound therapy applied on an open wound for secondary healing.pNPWT was documented to lower the incidence of surgical site infection (SSI) and wound dehiscence in closed laparotomy incisions –3. NotabThe financial burden of surgical site infection (SSI) is important and efforts should be made to reduce the incidence of SSI . HoweverTherefore, our objective was to determine the proportion of abdominal surgeons using pNPWT in their current practice, the indications they consider for pNPWT, the types of commercial devices used, the postulated limitations of the techniques and suggestions for improvement.The study consisted in an online survey developed on the software Evalandgo (Pro edition) , which wThe link to the online form was sent to members of the Swiss Surgical Society. Answers were retained only if all questions were answered and if the member were specialists in surgery. Students and/or residents without completed surgical qualification were excluded from analysis.The survey contained 22 questions, with both quantitative and qualitative aspects (Table S1). Briefly, participants were asked about their surgical qualifications, when they learned about pNPWT, the type of pNPWT devices available and used in their hospitals, the proportions of patients undergoing abdominal surgery who benefited from pNPWT, the types of wounds on which the participants applied pNPWT, the indications for pNPWT (in terms of risk factors for SSI), and their personal opinions about the eventual issues encountered with pNPWT and propositions for improvement.n (%) for categorical variables and as means (± SEM) for continuous variables. Descriptive analysis was performed using the PRISM software .Results were expressed as Nine hundred and seven surgeons have been solicited for the survey by the Swiss Surgical Society. One hundred and ten replied to the survey. Eleven participants were excluded; 5 for not being specialists in surgery and 6 for not completing the survey, leaving 99 patients for analysis. In terms of gender, 81 participants (81.8%) were males of 18 were females (18.2%). The mean age was 49.8 ± 1 years. Ninety-nine participants (100%) were specialists in general surgery, 41 (41.4%) were also specialists in visceral surgery and 14 (14.1%) had a European board certification for a subspecialty in surgery. The mean number of years of experience after obtaining the Swiss qualification for general surgery was 16.4 ± 1.1 years. The main field of surgical practice were general surgery for 42 (42.4%) participants, upper gastrointestinal surgery for 5 (5.1%), lower gastrointestinal surgery for 27 (27.3%), hepatobiliary surgery for 4 (4%), transplantation surgery for 2 (2%) and others for 19 (19.2%). Twenty-nine (29.3%) participants were working in a University Hospital, 49 (49.5%) in a regional hospital and 21 (21.2%) in a private clinic.Ninety-six (97%) participants have heard about pNPWT and three (3%) were not informed about the possibilities of pNPWT Fig. a. SeventMain reason for discontinuation of use was lack of observed effect, notably on the post-operative incidence of SSI.For those using pNPWT (70 participants), 47 participants (60%) had heard about pNPWT more than 5 years ago, 26 37.1%) between 1 and 5 years and 2 (2.9%) less than 1 year ago  and one (1.4%) participant used another system  had access to the PREVENA incision management system , 38 (54.3%) to the PICO single use negative pressure wound therapy system , 23 participants (32.9%) performed pNPWT using a customized system from usual NPWT (V.A.C.pNPWT was used on midline laparotomy by 63 participants (90%), closed stoma wounds (after stoma closure) by 21 (30%), closed perineal wounds by 20 (28.6%), Pfannenstiel incisions by 18 (25.7%), groin incisions by 16 (22.9%), subcostal incisions by 13 (18.6%), Mc Burney incisions by 3 (4.3%) and other incisions by 18 (25.7%)  participants, wound dehiscence for 41 (58.6%), incisional hernia for 14 (20%) and bad aesthetic aspect of the scar for 3 (4.3%). Four (5.7%) participants did not think that pNPWT was efficient in preventing any of these wound-related complications. The most efficient system was considered by the participants to be the PREVENA incision management system by 31 participants (44.3%), the PICO single use negative pressure wound therapy system by 20 (28.6%), a customized system from usual NPWT by 14 (20%) and another system by 3 (4.3%). The major limitations of pNPWT reported by participants were the cost of the therapy, the difficulties encountered when applying pNPWT on particular areas, such as the perineum or in close proximity to drains and/or stomas, and also lack of patient’s mobility due to the device. Of note, some participants reported the need for more evidence regarding the effect of pNPWT in preventing wound-related complications in abdominal surgery. As a consequence, suggestions for improvement to pNPWT were: better sealing, recyclable system, better adaptation to the perineum, smaller device, reduced cost and possibility to check the surgical wound through the dressing.In the present study, we showed that the majority of Swiss surgeons (97%) practicing abdominal surgery knew about pNPWT for prevention of wound-related complications after open abdominal surgery. pNPWT was widely available in participants’ hospitals, with the most common commercial devices thoroughly represented. However, 26.3% of participants have reported to have never used pNPWT in abdominal surgery. We note that the literature showing a beneficial effect of pNPWT in abdominal surgery on the incidence of SSI is recent  and timeMoreover, three participants stopped using pNPWT due to postulated lack of observed effect on the prevention of wound-related complications. This raises the question whether this lack of observed effect is merely due to an accumulation of unlikely events Below is the link to the electronic supplementary material.


Dynamic light scattering analysis revealed the particle size and zeta potential in the range of 385.1±2.45–762.8±2.05 nm and -22.4±0.55–31.2±0.96mV respectively. Fourier transform infrared (FTIR) spectroscopic analysis depicted the physicochemical compatibility, powdered x-ray diffraction (PXRD) analysis predicted the crystalline nature of pure drug and its transition into amorphous form within formulation. The differential scanning calorimetry (DSC) demonstrated the thermal stability of the formulation. The in vitro drug release study using dialysis membrane displayed the enhanced dissolution of diacerein due to the presence of hydrophilic carrier  followed by sustained drug release due to the presence of lipid mixture (lecithin and cholesterol). Ex vivo permeation studies depicted 3.50±0.27 and 3.21±0.22 folds enhanced flux of liposomal gels as compared to control. The acute oral toxicity study showed safety and biocompatibility of the system as no histopathological changes in vital organs were observed. These results suggests that proliposomes and liposomal derived gel are promising candidates for the solubility and permeability enhancement of diacerein in the management of osteoarthritis.The present study is associated with the development of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein. Proliposomes were developed by thin film hydration method and converted into the liposomal derived gel using carbopol-934 as a gelling agent. Formulations with varied lecithin to cholesterol ratios were investigated to obtain the optimal size, entrapment efficiency, and enhanced  Over the few decades, considerable attention has been given to the development of novel drug delivery systems. The novel drug delivery systems aim to deliver the drug at the target site to meet the requirements of the body . Novel din vitro and in vivo . Th. Th33]. The thermal analysis and physical state of diacerein in proliposomal formulations were ascertained from the DSC thermograms. The DSC thermograms of diacerein, their physical mixtures and formulations (D5PL and D11PL) are shown in The particle size of egg lecithin (D1PL-D6PL) and soy lecithin (D7PL-D12PL) based liposomal formulations were in the range of 385.1±2.45 nm-762.8±2.05 nm and 412.9±3.11nm-634.7±2.00 nm respectively . The parp<0.05).The polydispersity index (PDI) values of all liposomal formulations were less than 0.45, which indicates the mono-dispersity of PL derived liposomes. The zeta potential values of egg lecithin (-22.6 ± 0.61 mV to -31.2 ± 0.96 mV) and soy lecithin (-22.4 ± 0.55 mV to -30.9 ± 0.78 mV) based formulations  indicateThe transmission electron microscopic (TEM) images of the liposomes after hydration are shown in The EE of egg lecithin based liposomal formulations was in the range of 57.92±1.02% to 86.13±1.19% . Likewisp<0.05).Cholesterol is one of the important components used in the fabrication of proliposomes and liposomes and has a direct effect on the EE. Upon increasing the cholesterol contents the EE increases, as it provides vesicular stability to the liposomes. The aforementioned behavior is associated with a certain limit of the cholesterol concentration (D1PL-D5PL) and (D7PL-D11PL). But, when cholesterol content is above this limit, the entrapment efficiency decreases as in the case of D6PL and D12PL. The reason may be due to competition between the diacerein and cholesterol within the vesicle and the system will retain the increased cholesterol concentration due to its stable nature. A similar effect is also reported by Ning, M.-Y., et al., 2005 . The lipp<0.05).Whereas, the LC is the percentage of drug successfully loaded in the liposomes. The LC of the formulations was in the range of 6.43±0.85–8.79±0.74 as shown in in vitro release study highlighted that, at simulated gastric pH (pH 1.2) without enzymes, almost 20% of the drug was released from the system within 2 hours. The maximum drug release from the system (>90%) was achieved in 16 hours using a phosphate buffer of pH 6.8 without enzymes as a surrogate indicator of the intestinal medium shown in in vitro release profile of optimized formulations with the individual formulation showed a significant difference (p<0.05).The 2) is an indicator of the drug release model when it approaches unity. According to the modeling data, the drug release followed first-order release kinetics as the R2 were in the range of 0.9640–0.9854 (shown in The regression coefficient (Rshown in  which me-2h-1) versus time (hours) was plotted (p<0.05).Graph of percent drug permeation  and 3.21±0.22 (D11PL-G) folds enhanced permeation across excised Wistar rat skin by egg and soy lecithin based liposomal gels compared to the control. Also, an acute oral toxicity study endorsed that VDDS along with their phospholipids are non-toxic and biocompatible for the biological system. The phospholipids used (egg and soy lecithin) have a comparable effect on the physicochemical characterization of proliposomes, liposomes and liposomal gel whereas, cholesterol has a stabilizing effect on the vesicles. In brief, the developed proliposomes and liposomal gels significantly enhanced the solubility and permeability of diacerein and can provide better management regarding osteoarthritis. In the future, the current study may be extended to the in vivo animal study and humans based clinical evaluation for management of osteoarthritis.The diacerein loaded proliposomes and liposomal derived gels were successfully developed with improved solubility and permeability. The S1 Data(PDF)Click here for additional data file.


Parmaturus melanobranchus was collected from the South China Sea. The complete mitochondrial genome of the specimen was sequenced using Illumina Hiseq platform and assembled with Geneious and Trinity. The mitogenome is 16,687 bp long with a base composition of 30.4% A, 14.1% G, 23.5% C and 32.1% T, respectively. A total of 37 genes were predicted containing 13 protein-coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes. This is the first complete mitochondrial genome published of this species.A rare specimen of  And a tissue sample was deposited at the Lab of Molecular Systematics and Ecology, Shanghai Ocean University, Shanghai, China. The specimen was identified as Parmaturus melanobranchus, a rare species of cat shark, based on the identification criteria defined by Chan et al.  and Trinity  from Sangon Biotech . An Illumina library was prepared following Meyer and Kircher (2010) and the mitochondrial DNA was enriched and sequenced using an Illumina Hiseq platform. Geneious 7.1.9  strand and 9 genes were on the light (L) strand. The base composition of the mitogenome was 30.4% A, 14.1% G, 23.5% C and 32.1% T, with a G + C content of 55.6%.The mitochondrial genome of P. melanobranchus (LC020831) collected by the Okinawa Churaumi Foundation. Actually there is only one-nucleotide difference between the 181 bp sequence of 12S gene of these two specimens. We also reconstructed a phylogenetic tree of the 13 protein-coding genes (PCGs) of 9 sharks (see details and GenBank numbers in There was no previous complete mitochondrial genome of this species or genus available on GenBank. We downloaded all the available mitochondrial data of this genus and reconstructed a supermatrix tree using MEGA X (see details and GenBank numbers in


The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs. At early time points after vaccination with a single dose or two doses of the BNT162b2 mRNA COVID-19 vaccine, breakthrough SARS-CoV-2 infections can be disproportionately caused by the B.1.1.7 or B.1.351 variants of concern, underlining the need to ensure rapid and complete vaccination. However, concerns have emerged regarding the effectiveness of vaccines against various SARS-CoV-2 strains. In particular, three strains have recently been defined as VOCs by the WHO : the B.1.1.7 strain (first detected in the UK), the B.1.351 strain (first detected in South Africa) and the P.1 strain (first detected in Brazil). Accumulating evidence suggests that the B.1.1.7 strain spreads more rapidly than the original circulating strain and leads to substantially more infections4.Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently underway worldwide, providing hope that the coronavirus disease (2019) COVID-19 pandemic may soon be mitigated. In Israel, vaccination commenced on 20 December 2020, primarily with the BNT162b2 mRNA vaccine, and by mid-March 2021, more than 80% of the eligible population  were vaccinated with at least one dose. In clinical trials, the BNT162b2 mRNA vaccine was shown to be 95% efficacious in preventing symptomatic disease; a similarly high protective effectiveness has also been found in real-world settings in Israel6), yet the evidence has been mixed. Using engineered viruses and/or sequences, laboratory studies have shown that neutralization of B.1.1.7 by BNT162b2-vaccine-elicited sera was either similar to or slightly reduced as compared to neutralization of early circulating isolates12 with or without the globally dominant D614G alteration13. Conversely, a significant reduction in neutralization of B.1.351 was observed12, while other studies suggested neutralization remained relatively high against both B.1.1.7 and B.1.351 (ref. 14). T cell responses, which are not captured by neutralization studies, were also shown to remain stable against these variants following vaccination15. Thus, it remains unknown whether VOCs can mediate BNT162b2 vaccine breakthrough in real-world settings, in which the vaccine elicits persistent antibody and T cell responses. Here, we tested the hypothesis that the B.1.1.7 and B.1.351 strains are able to overcome BNT162b2 mRNA vaccine protection, by comparing their distributions in infected vaccinated individuals and in infected non-vaccinated individuals.Concerns have emerged that the B.1.351 and P.1 strains are able to overcome previous immunity to SARS-CoV-2  was matched with an unvaccinated infected individual (control) who tested positive on a similar date (±3 days) and had similar demographic characteristics  to reduce bias associated with differential exposure , the largest health care organization in Israel, which insures 4.7 million patients (53% of the population). We divided these individuals into two categories: individuals who had a positive PCR test that was performed between 14 days after the first dose and 6 days after the second dose (denoted as the dose1 group); and individuals who had a positive PCR test that was performed at least 7 days after the second vaccine dose (denoted as the dose2 group). The definitions of these two categories were chosen to match the original BNT162b2 vaccine efficacy studyexposure . Next, w13. We did not find evidence for the increased presence of any additional alterations that are not lineage-defining alterations of B.1.1.7 or B.1.351.We next used a stringent method of lineage assignment for each viral sequence . Aside f16.When examining lineage frequency across time, we noted that B.1.1.7 was the predominant strain of the virus in Israel over the entire sampling period (712/813 sequences), increasing in frequency over time Fig. . ConversOn the basis of previous results from neutralization assays, we hypothesized that B.1.1.7 may be slightly vaccine resistant as compared to WT, whereas B.1.351 may be more vaccine resistant when compared to both B.1.1.7 and WT. Under this hypothesis of ordered resistance, we performed our statistical analyses first on the B.1.1.7 strain, while excluding B.1.351 sequences , and then compared the B.1.351 with the B.1.1.7 and WT sequences combined Fig. . We use P = 0.38), but a significantly higher proportion of B.1.351 was observed in dose2 cases versus unvaccinated controls . Of note, about half of dose2 cases tested positive on days 7–13 after the second dose, and about half tested positive 14 days or more after the second dose  of 6:4; one-sided exact McNemar test, P = 0.006). For B.1.351 in the dose1 category, the sparsity of data (one infection in each category) precluded statistical analysis  value ). An additional dose1 control sequence was also ambiguously classified . Although this remains to be tested in a more widespread manner, it suggests that neutralization studies may be valid as a prompt first step before the establishment of real-world studies in the case of the emergence of new SARS-CoV-2 VOCs.Our results show that there is an increased proportion of VOCs in vaccine breakthrough infections that occurs within two particular windows of time. An increased proportion of B.1.351 was found in individuals fully vaccinated with BNT162b2, 7–14 days after the second dose, as compared to the matched unvaccinated controls. Furthermore, an increased proportion of B.1.1.7 was found in partially vaccinated individuals, 14 days after the first dose until 6 days after the second dose, as compared to the matched unvaccinated control, yet we find no evidence for increased breakthrough rates of B.1.1.7 a week or more after the second dose , yet we did note higher VL in B.1.351 infections, while noting lower VL in vaccinees as compared to unvaccinated individuals . More research is required to further understand the evolutionary pressures operating on VOCs, in Israel, and around the world. At the time of revision of this paper, May 2021, we note that case counts in Israel have dramatically dropped to around 35 cases per day in a population of ~9 million (ref. 31), suggesting that while vaccine breakthrough infections at particular windows of time may be more frequent with the VOCs B.1.1.7 and B.1.351, mass vaccination with two doses controls and contains their spread.We were reassured to observe the low frequency of B.1.351 across time Fig. 16. Of noion Fig. . Owing tThe study was approved by the CHS institutional review board (no. 0016-21-COM2) and was exempt from the requirement for informed consent. The study was further approved by the Tel Aviv University ethics committee (0002706-1).Data for this study were obtained from CHS’s data repositories , with slight modifications detailed below. Briefly, reverse transcription and multiplex PCR was performed in two amplicon pools, and NEBNext Multiplex Oligos for Illumina were ligated to allow for sequencing. All samples were run on an Illumina MiSeq using 250-cycle V2 kits at either the Technion Genome Center (Israel) or at the Genomics Research Unit at Tel Aviv University (Israel). We and others have previously noted amplicon dropout of amplicons 74 and 76 (ref. 32), both of which cover the spike gene, and in particular some of the lineage-defining alterations of B.1.1.7 and B.1.351 (such as E484K and N501Y). To increase the sequencing yield of these amplicons, we doubled the primer concentrations of both amplicons in our primer pool and lowered the annealing–extension temperature to 63 °C.Following matching, RNA from cases and controls was obtained from the main testing laboratories of CHS, with one major limitation: only samples with Ct values of 33 or lower were collected. Ct values were averaged over all genes tested (per laboratory). The dates of the samples ranged from 23 January 2021 to 7 March 2021  using our AccuNGS V1 pipeline34 that is based on BLAST35, using a particular stringent e-value of 10−30. We then set out to determine the consensus sequence of each sample. Typically studies report a majority-rule consensus sequence; that is, the consensus base at each position in the genome is the base that most reads (>50%) support. However, the biological meaning of variable positions where more than one base is observed is complex, especially if such positions are abundant: they may indicate within-host variation, they may indicate multiple genotype infection, they may indicate sample contamination, and they may indicate sequencing errors. To overcome these limitations, we constructed two consensus sequences for each sample, one based on majority rule, and a more strict consensus sequence where we required at least 80% of reads to support a given base. Bases with lower support were assigned an N (ambiguous base). We also noted some regions with fluctuating ambiguity: if a continuous subsequence of length 20 or lower was flanked on both ends by ambiguous bases, we masked out this entire subsequence by assigning it with N, under the assumption it represents unreliable sequencing. In both types of consensus sequencing assignments, we required sequencing coverage of at least ten reads. Finally, we used the Pangolin v2.2.2 software (https://github.com/cov-lineages/pangolin) to assign lineages for each consensus sequence using the Pango nomenclature (pangoLEARN 2021-02-06)36, which requires that at least 50% of bases sequenced are unambiguous. After verifying the type of lineages we obtained, we labeled all consensus sequences as either B.1.1.7, B.1.351 or WT. Samples for which Pangolin labels of the strict and majority-rule consensuses did not coincide were discarded. Thirty-two pairs in which one sample did not undergo successful sequencing were discarded from the paired analyses , was located within the B.1.351 clade on the phylogenetic tree. Its pair was classified as B.1.1.7, and we included this pair in our extreme scenarios analysis , Matplotlib v3.2.1 (ref. 39), Seaborn v0.10.1 and ggplot2 (ref. 40) were used during the data analysis and visualization.R v4.0.4, Python v3.7.4, pandas v0.24.2  McNemar’s test was used to compare breakthrough of a variant in partially or fully vaccinated individuals. For the analysis of B.1.351, all other variants were defined as the reference group, while for the B.1.1.7 analysis, we excluded any paired observation that included B.1.3.5 , while any other variant was defined as the reference. A conditional logistic regression was used as a sensitivity analysis to include age as a possible confounder in case that matching was not sufficient, under the assumption that it was sometimes only partially mediated through matching. The regression was performed only on the dose1 B.1.1.7 analysis, as not enough data were available in other categories. All analyses were conducted with R software version 4.03 and the survival and exact2x2 packages.https://www.gisaid.org/) from August onwards were downloaded, focusing on high-quality sequences with 10% or less ambiguous sites. Of these sequences, owing to computational limitations, we sampled the most distant 100 WT sequences and 50 B.1.1.7 sequences, and included all available B.1.351 sequences (Supplementary Table MN908947.3) was added on as well, and these sequences were combined with sequences from this study that contained at most 10% ambiguous sites. Alignment was performed using Mafft v7.300b (ref. 41) with default parameters. Next, a maximum-likelihood phylogeny was reconstructed using PhyML v3.0_360-500M (ref. 42) with default parameters as well, and the tree was rooted using the MN908947.3 sequence from the original outbreak first detected in Wuhan. The ggtree v2.5.1 package was used to visualize the phylogenetic trees.All Israeli sequences available on GISAID (Further information on research design is available in the Any methods, additional references, Nature Research reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41591-021-01413-7.Supplementary InformationSupplementary Figs. 1–6.Reporting SummarySupplementary Table 1A list of all sequence accession numbers used in this study and their metadata.Supplementary Table 2A list of all additional publicly available Israeli sequences from GISAID used in the study.


Type 2 diabetes (T2D) is a known risk factor for cardiovascular disease (CVD), and CVD is a major cause of mortality in patients with T2D. The CAPTURE study investigated the contemporary (2019) prevalence of established CVD in adults with T2D around the world. We report the findings from Brazil.The multinational, non-interventional, cross-sectional CAPTURE study was conducted across 13 countries from five continents. The current manuscript explores data for the CAPTURE study sample in Brazil. Standardized demographic and clinical data were collected from adults with T2D aged ≥ 18 years attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data were analyzed descriptively.2 ; 59% were female. The CVD prevalence and atherosclerotic CVD prevalence in the Brazil sample were 43.9%  and 37.6% , respectively. The majority of patients with CVD had atherosclerotic CVD (85.8%). For the specific CVD subtypes, coronary heart disease prevalence was 27.9% , heart failure was 12.4% , cerebrovascular disease was 8.7% , and carotid artery disease was 3.4% . Glucagon-like peptide-1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit were prescribed to 15.5% of patients with CVD, compared with 18.4% of patients without CVD.Data from 912 adults with T2D were collected in the CAPTURE study in Brazil, with 822 patients from primary care and 90 patients from specialized care. Median (interquartile range [IQR]) patient characteristics were as follows: age 64 years , diabetes duration 11 years , glycated hemoglobin 7.7% , and body mass index 29.5 kg/mCAPTURE was the first multinational, standardized study to provide contemporary data on CVD prevalence in adults with T2D in Brazil, and it demonstrated that almost one in two adults with T2D had established CVD. Except for carotid artery disease, the prevalence of all CVD subtypes in adults with T2D in Brazil appeared higher than the global CAPTURE prevalence.Trial registration NCT03786406, NCT03811288The online version contains supplementary material available at 10.1186/s13098-021-00775-9. The prevalence of diabetes, and its associated morbidity and mortality, has been increasing globally . AlthougDiabetes is a known risk factor for cardiovascular disease (CVD). Results of a cross-sectional study in Brazil estimating the cardiovascular (CV) risk in 1382 patients with type 2 diabetes (T2D) reported that the majority of patients were at a high risk of coronary heart disease (CHD), in particular those patients with chronic microvascular complications, or those who are overweight or obese . In a seBased on the increasing evidence that CVD is a major cause of mortality in patients with T2D , 8, therThe CAPTURE study  was a non-interventional study using a standardized methodology to assess the prevalence of CVD among adults with T2D in 13 countries across the world . Here, wThe study design of CAPTURE, a multinational, non-interventional, cross-sectional study conducted across 13 countries, has previously been described . The curThe protocol was approved by the ethics committee at each participating trial site and the study was conducted in accordance with the provisions of the Declaration of Helsinki , the IntLocal medical affairs personnel employed by the sponsor provided information on the management of people with T2D in Brazil, including the types of physicians and practices managing patients with T2D. Information was also obtained from the national coordinating investigator and from literature searches. Sites deemed to be representative of the management of T2D in Brazil were invited to participate and to complete a feasibility questionnaire. Sites that accepted the invitation were included in the study.Physicians at participating sites invited consecutive adults attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019 to participate within a 90-day time period. Eligible participants were aged 18 years and older at the time of informed consent, with a diagnosis of T2D ≥ 180 days prior to providing informed consent. Exclusion criteria were a diagnosis of type 1 diabetes, congenital heart disease or malformation, previous participation in this study, mental incapacity, unwillingness, or language barriers precluding an adequate understanding or cooperation.Data, including demographic, anthropometric and clinical parameters, selected medical history, GLAs, and CV medications, were collected from patients’ medical records by physicians or appropriately qualified and trained individuals. Data on medications only included those currently in use or those discontinued within ≤ 3 months. GLAs were categorized according to CV benefit, as demonstrated in CVOTs, and based on the 2020 American Diabetes Association guidelines; the GLAs with CV benefit included three GLP-1 RAs  and three SGLT2is  .The primary objective of CAPTURE was to assess CVD prevalence in adults with T2D across 13 countries and individually, including Brazil, using a standardized methodology. This report focuses on the CVD prevalence data from Brazil. Furthermore, the use of CV medications and GLAs with demonstrated CV benefit in Brazil was also assessed. CVD was defined as the presence of any of the following subtypes: cerebrovascular disease, carotid artery disease, CHD, peripheral artery disease (PAD), heart failure, cardiac arrhythmia, or aortic disease. Additionally, atherosclerotic CVD (ASCVD) was designated as a subset of CVD subtypes and included the following diagnoses: cerebrovascular disease, CHD, PAD, or carotid artery disease   for the overall CAPTURE population in Brazil, in addition to subgroups stratified according to the presence of CVD , were analyzed descriptively only and not statistically due to the study design. Calculated prevalence estimates were weighted by primary care/specialist care setting within Brazil.Data from 912 patients with T2D were collected across 21 sites in the CAPTURE study in Brazil, with 822 patients attending primary care sites and 90 attending specialist care sites. Participating trial sites recruited an average of 43.4 patients (range: 6 to 100)  7.7% , and body mass index (BMI) 29.5 kg/m2 . Hypertension was present in 80.9% of the overall population and kidney dysfunction (estimated glomerular filtration rate [eGFR] < 59 mL/min/1.73 m2) in 35.4%  data for age were 64.0 years 57.0; 71.0), with diabetes duration 11.0 years , glycated hemoglobin  of CVD was 43.9%  Table . SimilarIn the Brazil sample, the CVD subtypes with the highest weighted prevalence (95% CI) were CHD 27.9% , heart failure 12.4% , and cerebrovascular disease 8.7%  had ASCVD. Analyzing the CVD subtypes in this CVD patient group, CHD was the most common subtype , and PAD (19.0% [n = 76/400]).2: 44.5% vs 29.0%), in addition to a higher proportion of smokers (current/previous: 46.4% vs 27.1%), although differences between the subgroups were not formally tested. Prevalence of microalbuminuria also appeared higher among the CVD versus the Non-CVD subgroup (40.2% vs 23.5%), as were the microvascular complications of retinopathy (27.8% vs 16.0%), nephropathy (38.0% vs 25.9%), and neuropathy , had a lower proportion of females (47.5% vs 68.0%), and a higher proportion with hypertension (89.0% vs 74.5%) and kidney dysfunction . Oral antidiabetic drugs were used by 88.9% of the overall population, with a numerically lower proportion of patients in the CVD group receiving oral antidiabetic drugs (86.0%) compared with those in the Non-CVD group 91.2%). Insulin was used by 40.8% of the overall population, 47.0% of the CVD population, and 35.9% of the Non-CVD population , acetylsalicylic acid (54.3%), and angiotensin II receptor blockers (54.0%), while the most frequently prescribed CV medications in the Non-CVD group were statins (56.4%), angiotensin II receptor blockers (44.5%), and thiazides  of all patients recruited to the CAPTURE study, and the second highest weighted prevalence of CVD . Analysis of data for the CAPTURE Brazil sample demonstrated that almost one in two adults (43.9%) with T2D had established CVD, which is a higher prevalence than that seen in the overall multinational sample (34.8%) (16).In Brazil, ASCVD was highly prevalent among patients with T2D  and among those with T2D and CVD . Within the subtypes of CVD, CHD was the most prevalent one, with CHD, heart failure, cerebrovascular disease, and PAD being more prevalent compared with other subtypes , albeit at lower rates than ASCVD, as ASCVD is a combination of several CVD subtypes. The prevalence of all CVD subtypes were higher in the Brazil sample compared with the multinational sample, with the exception of carotid artery disease, which was lower in the Brazil sample than in the multinational sample (3.4% vs 8.4%) . It is p2) was seen in more patients in the Brazil sample (35.4%) compared with the multinational sample (21.0%). The median HbA1c levels in Brazil appeared slightly higher versus the multinational sample , which ectively .It is interesting to note the relatively low use of statins (78.5%)  in the CVD group, given the increased emphasis on lipid-lowering (and ongoing prevention of atherosclerotic events) in the 2017 guidelines . NeverthUse of any GLA with proven CV benefit (GLP-1 RA and/or SGLT2i) was lower in the Brazil sample than in the overall multinational study population . MoreovThere may also have been medication-specific reasons why the rate of the prescription of SGLT2is was lower in the Brazil sample compared with the global sample. For example, in the CAPTURE global sample, a total of 91 patients were treated with the SGLT2i canagliflozin, which has proven CV benefit ; howeverLinked to differences in prescribing patterns, a previous sub-analysis of an online survey explored the perceptions and routines of patients with T2D and physicians in Brazil, compared with other countries  . PreventThe CAPTURE study in Brazil had a number of limitations. There was the potential for selection bias in this cross-sectional study that may have resulted in study sites and a population sample that were not representative of the management of T2D in Brazil, and the sample size of patients with T2D in secondary care setting is small. Relative to the size of the T2D population in Brazil, the CAPTURE study sample was small (n = 912 patients). Data were not formally tested statistically, limiting the robustness of any comparisons. Finally, this non-interventional study did not screen or adjudicate for the presence of CV complications; thus, there may have been under-or over-diagnosis of CVD.1c levels should be strived for. The results also show a lower use of GLAs with demonstrated CV benefits in the Brazil sample versus the multinational sample, despite national guidelines advocating their use in patients with T2D and ASCVD or at very high risk of CVD [The CAPTURE study provides valuable contemporary cross-sectional data on CVD prevalence in Brazilian patients with T2D, demonstrating that almost one in two have established CVD, of which the majority have ASCVD. All CVD subtypes had higher prevalence in the Brazil sample compared with the multinational sample, with the exception of carotid artery disease. Standard therapeutic strategies to ameliorate CV risk factors appear to be utilized in this population (i.e. statin and aspirin treatment), although these rates could be improved. Likewise, improvements in HbAk of CVD . ProvidiAdditional file 1: Table S1. Definition of CVD diagnoses in the CAPTURE study. Table S2. List of participating trial sites. Table S3. Use of glucose-lowering agents in the CAPTURE study population stratified by CVD status in Brazil. Table S4. Proportion of patients receiving GLP-1 RAs and SGLT2is with proven CV benefit (Brazil). Table S5. Use of CV medications in the CAPTURE study population stratified by CVD status in Brazil. Figure S1. GLAs with proven CV benefit use in the CAPTURE Brazil sample stratified by CVD status.


The most important prognostic factor in transfusion-dependent beta-thalassemia is cardiac involvement which is usually evaluated with echocardiography.In this cross-sectional study (April 2011 to April 2012), conventional echocardiography was used to assess myocardial performance and valvular involvement  for right and left heart abnormalities in transfusion-dependent beta-thalassemia.Among the 60 patients, 43 cases had heart problems, 26 (43.3%) of them had left myocardial dysfunction and 11 (18.3%) of them had right myocardial dysfunction, 3 cases had both RV and LV myocardial dysfunction, . In patients with right myocardial dysfunction, 4 cases had pulmonary hypertension (PH) and 3 had both sided myocardial dysfunction. LVMPI and RVMPI significantly increased in patients with cardiac involvement (p<0.001). Serum ferritin levels in patients with and without cardiac involvement were 2427±1788 ng/ml and 1573±592 ng/ml, respectively (P=0.008). All 4 patients who had PH, had been splenectomized. In splenectomized and non-splenectomized patients, LVMPI was 0.37±0.11 and 0.38±0.1 (P=0.589), RVMPI was 0.3±0.07 and 0.25±0.39 (P=0.004), and TR gradient (TRG) was 28±11.8 mmHg and 19.7±5.2 mmHg (P=0.033), respectively. Mean ferritin level in patients with a history of splenectomy (n=31), was 2525±1968 ng/ml and in patients without the history of splenectomy (n=29) was 1821±947 ng/ml (P=0.082).In addition to left-sided heart involvement, conventional echocardiography revealed right-sided heart involvement in transfusion-dependent thalassemia patients which did not correlate with serum ferritin level in splenectomized patients. Thalassemia is a genetic disorder with an inheritance of autosomal co-dominant genes, which generates a heterogeneous group of abnormalities in hemoglobin biosynthesis , 2, and Evaluation of specific heart involvements in conventional echocardiography can help to early diagnosis of these problems. Recently, a variety of right myocardial involvement has been reported in transfusion-dependent beta-thalassemia, which requires special attention -12. DataPatients’ collection: In this cross-sectional study, which was conducted for one year from April 2011 to April 2012, 60 beta-thalassemia patients with transfusion dependency were studied. According to research committee approval number, “89-10-35-16”, patients with thalassemia who were regularly transfused and received chelation, were selected and all demographic information  and echocardiographic findings were recorded in the questionnaires. Inclusion and Exclusion criteria: All patients with transfusion-dependent thalassemia who referred to the thalassemia clinic of Besat Hospital, city of Hamedan, were studied. Exclusion criteria were: non-beta thalassemia patients, non-transfusion dependent beta-thalassemia, an association of congenital heart disease and other congenital malformations.2) MR, AS, and AI were considered as cardiac involvements in thalassemia patients, while mild TR and PI, which were used for the calculation of pulmonary artery pressure, were not considered as valve lesion. Pathologic MR  was considered a holosystolic wave with more than 3 meters/second velocity. Continuous Doppler echocardiography of the tricuspid valve was used to calculate tricuspid regurgitation gradient (TRG). TRG above 35 mmHg and end-diastolic PI above 15 mmHg were considered as pulmonary hypertension (PH) and in case the gradient was greater than half of the aortic systolic pressure, PH was considered severe. Serum ferritin level was measured through the Elisa method by an Elisa reader awareness device manufactured by the USA and a Delaware kit. The information inserted in the checklists and questionnaires was analyzed by SPSS (Version 16) software. Quantitative variables were described as mean +/_; standard deviation and quality variables were described as frequency and percentage. Data were analyzed using t-test, correlation coefficient, x2 and a p-value less than 0.05.Patients were evaluated for cardiac status by conventional echocardiography, which was performed with Mylab50 and 60 devices, using a 3-4 MHZ phased array probe. Ejection fraction (EF) was obtained by M-mode echocardiography, in which less than 55% was considered as left ventricular systolic dysfunction. A global diastolic and systolic function index ) was calculated, based on transvalvar doppler echocardiography with the formula: "a-b/b", at which "a" is the time of closure to the opening of the mitral valve for the left side and the time of closure to the opening of tricuspid valve for the right side and “b” is the time of blood ejection from aortic valve for the left side and pulmonary valve for the right side of the heart. LV and RV myocardial dysfunction with MPI greater than 0.45 for the left side of the heart and greater than 0.35 for the right side of the heart were defined. Valve gradients were calculated using continuous doppler of each valve, based on Bernoulli formula  patients were males and 27(45%) were females. The oldest was 37 years old  and the youngest was 3 years . The highest age frequency was 19, with 71.6% relative frequency. 39 (65%) patients were taking only deferoxamine , 20 (33.3%) patients were using deferasirox  as the main chelator, and only one (1.7%) patient was using deferiprone (L1). The earliest onset of blood transfusion was in the first month of age and the latest blood transfusion was at the age of 9 with an average age of 1.5±1.67 years. The minimum age of onset of chelation therapy was one year, the maximum age was 14, and the average was 4.2±2.53 years. The onset of chelation therapy after blood transfusion was immediate in four patients, with a maximum interval of 9.5 years and a mean of approximately 2.72 years. The mean duration of transfusion therapy before the diagnosis of heart involvement was 18.07±7.8 years, and it was 15.84±6.7 years in patients without cardiac involvement until the present study (P=0.2). The mean duration of chelation therapy until the onset of cardiac involvement was 14.6±9.7 years in patients with heart disease and it was 13.1±4.8 years in patients without heart involvement (P=0.3). The mean serum ferritin level in patients with heart involvement was 2427±1788 ng/ml and in patients without cardiac involvement was 1573±592 ng/ml (P=0.008). The lowest amount of ferritin in patients with heart involvement was 258 ng/ml and the highest value was 11530. A total of 43 patients had abnormal cardiac findings . The meaFrequency of types of abnormal cardiac findings in thalassemia patients: 43 (71.6%) patients had abnormal cardiac findings according to our definition, including 21 (48.8%) male patients and 22 (51.2%) female patients, in which 26 (43.3%) of them had LV MPI (Tei index) ≥ 0.45, and 11 (18.3%) patients had RVMPI greater than 0.35  cases had LVMPI and RVMPI greater than 0.45 and 0.35 respectively. 9 (15%) patients had pathologic MR, which their right and left MPI were within the normal range. Among those with abnormal LVMPI, 9 (15%) patients had E/A ≥1.8, 3 (5%) patients had EF less than 50, 3 (5%) patients had aortic insufficiency, one (1.7%) case had aortic stenosis, and one (1.7%) case had pericardial effusion. Among those with abnormal RVMPI, 3 patients (5%) had mild PH and one (1.7%) patient had severe pulmonary hypertension. Transvalvular continuous Doppler echocardiography studies showed: TR in 29 (46.7%) patients, MR in 18 (30%), AI in 3 (5%) patients and AS in one (1.7%) case. Pearson correlation showed a correlation between ferritin level and LVMPI with P=0.005  and corrChronic anemia in thalassemia major  has a prIn this study, which is conducted on 60 patients with transfusion-dependent beta-thalassemia using conventional echocardiography, left heart myocardial dysfunction was seen in 43.3% of patients, based on LVMPI , while only 5% of patients had left ventricular ejection fraction abnormality, based on LVEF (as an LV systolic function index). 9 patients 15%) had a mean mitral E/A ratio greater 1.8, which may be seen in diastolic myocardial dysfunction. This finding may express that MPI in this patients was more valuable in diastolic dysfunction than systolic dysfunction. Besides, this study shows that the myocardial performance index in conventional echocardiography was significantly disturbed in the right side of the heart as well as the left side and can be used as a good marker for right heart myocardial dysfunction. Among the 11cases with right myocardial dysfunction, eight patients had isolated right-sided heart problems, 4 of whom were associated with increased pulmonary artery pressure (6.6%), which was close to the percentage obtained in another study in Iran (4.5%) . As ther% had a mIn the present study, there was a clear relationship between the level of ferritin and cardiac involvement, as reported in many other studies. It means that overall the higher serum ferritin levels are associated with a higher risk of cardiac damage. In the present study, there was no significant difference between the level of ferritin and the total amount of blood transfusion per year in patients, which may be due to other mechanisms that increase our patients’ ferritin levels  or it maAccording to LVMPI , 38.7% of splenectomized patients had left myocardial dysfunction, which was not significant in comparison with non-splenectomized cases. In a recent study, researchers used mitral valve filling parameters, left atrial volume index based on cardiac MRI (CMR), left ventricular diastolic dysfunction in patients with splenectomy was evident . Increased iron deposition in the heart, based on the T2 CMR reports in patients with the history of splenectomy has been reported in some articles . In anotIn the present study, although 32.2% of patients with splenectomy had right cardiac dysfunction based on RVMPI criterion, approximately 91% of patients with right ventricular dysfunction had a history of splenectomy (P=0.004) and all four patients with increased pulmonary artery pressure (PH) had been splenectomized, and given that left ventricular dysfunction and high serum ferritin elevation in these patients were not clear, other mechanisms have been suggested for the cause of PH in these patients . PlateleIn addition to left-sided heart involvement, conventional echocardiography revealed right-sided heart involvement in transfusion-dependent thalassemia patients. While in patients with history of splenectomy, right myocardial dysfunction and increased pulmonary artery pressure without correlation with serum ferritin level can be seen.


Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected.P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 . Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP. An individual patient meta-analysis was performed on the gametocytocidal and transmission-blocking activities of single-dose primaquine. Gametocyte persistence and infectivity depended on the artemisinin-combination therapy that primaquine was administered with. Primaquine’s transmission-blocking effects were achieved at 0.25 mg/kg. Plasmodium falciparum gametocytes. Mature gametocytes are responsible for transmission of infection from humans to mosquitoes, and they remain largely unaffected by antimalarial treatment, including ACTs [Antimalarial regimens based on artemisinin and its derivatives, artemisinin-based combination therapies (ACTs) have been adopted widely as first-line treatment of uncomplicated malaria. Despite highly efficient clearance of asexual stage parasites and early gametocytes , 2, ACTsing ACTs . As a reing ACTs , 6 and ting ACTs , 7, 8. Aing ACTs .Plasmodium vivax and Plasmodium ovale infections, has been recast as a viable treatment strategy to reduce P. falciparum transmission. The ability of PQ and its predecessor plasmoquine to stop P. falciparum infectivity to malaria vectors has been known for many decades [Primaquine (PQ), a drug that is used routinely for the radical cure of  decades , 13. In  decades . To miti decades . The saf decades , 15. MulWe conducted a systematic review and individual patient data (IPD) meta-analysis of clinical trials to quantify the ability of single-dose PQ given in combination with different ACTs to clear gametocytes and block transmission, and to compare efficacies of different combinations.P. falciparum infection or asymptomatic parasite carriers containing at least 1 study arm with a combination of a blood schizonticide and a single dose of PQ; (2) patient demographics and information on dosing (mg/kg) of the blood schizonticide and PQ were available; (3) transmission potential was assessed by weekly gametocyte carriage  using molecular methods and/or by membrane feeding assay conducted on day 0 and any day post treatment; and (4) patients were followed up at least until day 14. In the eligible studies, non-ACT study arms, which were randomized to receive PQ or not, were also included in the analysis as they contributed to the overall estimate of PQ effect.Details of the systematic review (PROSPERO CRD42019126710) are provided in the All data included in this analysis were obtained in accordance with the laws and ethical approvals applicable to the countries in which the studies were conducted, and were obtained with the knowledge and consent of the individual to which they relate. Data were fully anonymized either before or during the process of uploading to the WorldWide Antimalarial Resistance Network repository. Use of existing data that are fully anonymized and that researchers cannot trace back to identifiable individuals does not require the review of the Ethics Committee under the guidelines of the Oxford University Research Ethics Committee.Statistical analyses were carried out according to an a priori statistical analysis plan . The preData from membrane feeding experiments were analyzed using logistic regression to identify predictors of (1) probability of a participant infecting at least 1 mosquito, and (2) probability of a feeding mosquito being infected. Random intercepts were included to account for multiple measurements per patient (1) or clustering within a membrane feeding experiment (2).Additional details such as predictors considered in each of the regression models and assessment of risk of bias analysis are given in Pfs25, Pfs230p, and Pfg377 mRNA. In addition to sexual-stage specific parasite detection, 3 of these studies also included data from membrane feeding experiments, where infectiousness was directly quantified by feeding mosquitoes on infected blood and assessing oocyst development 1 week later. G6PD deficiency was assessed using fluorescence spot test in 4 studies, rapid diagnostic test in 5 studies, or genotyping in 3 studies. All studies, except 1 from Colombia, were conducted in Africa at sites with varying transmission intensities. Administration of PQ was randomized and compared to a no-PQ arm in all studies except for 1 in which the dose of PQ was increased sequentially (study 8). A total of 66.7% (1718/2574) of participants received a dose of PQ , of whom 355 (20.7%) were treated on day 0, 1241 (72.2%) on day 2, and 122 (7.1%) on day 3. Of the 1718 individuals treated with PQ, 477 (27.8%) patients received the WHO-recommended 0.25-mg/kg dose and 474 (27.6%) received a 0.40-mg/kg dose. Other doses tested included 0.0625, 0.1, 0.125, 0.2, 0.50, and 0.75 mg/kg . Six studies’ protocols excluded individuals with G6PD deficiency  with 19.7% (504/2563) younger than 5 years. Most of the 2574 study participants were treated with artemether-lumefantrine (AL)  or dihydroartemisinin-piperaquine (DP) . Other treatments administered included: artesunate-sulfadoxine-pyrimethamine (ASSP)  and sulfadoxine-pyrimethamine-amodiaquine (SPAQ) . At enrolment, 14.5% (366/2525) of patients presented with anemia (hemoglobin level below 10.0 g/dL), 12.8% (239/1860) with fever, and 5.8% (139/2392) had more than 100 000 parasites/µL ; 12.2%  (P = .308) between day 7  and day 14 .In total, 632 (31.3%) patients presented without detectable gametocytes on enrolment, of whom 481 (76.1%) were assessed weekly for gametocyte carriage during the first 14 days of follow-up. Detectable posttreatment gametocytemia was present in 12.9% (39/302) of patients treated with PQ compared to 19.6% (35/179) of those not treated with PQ  . The effP < .001). The corresponding proportions of individuals who were still gametocytemic on day 14 were 11.4% (106/931) and 42.9% (202/471), respectively  (P = .021), while those treated with SPAQ were more likely to carry gametocytes . On day 14, only the baseline gametocyte density and antimalarial treatment were associated with gametocyte carriage. After adjustment for these factors, a higher dose of PQ was associated with lower prevalence of gametocyte positivity on days 7 and 14 . This dose effect translates to an AOR of 0.40  for day 7 gametocyte carriage and AOR 0.26  for day 14 gametocyte carriage for patients who received 0.25-mg/kg dose of PQ compared to those who did not receive PQ.At enrolment, 1754 (68.7%) patients had gametocytes detected by molecular methods. Among those patients treated with PQ, 23.4% (258/1101) had gametocytes detected on day 7 compared to 57.4% (316/551) of those not treated with PQ  . In mult < .001) . CompareP = .010 for day 7 and P < .001 for day 14). Among individuals treated with AL, most of the reduction in gametocyte carriage probability was achieved with the recommended 0.25-mg/kg PQ dose, whereas in individuals treated with DP higher doses of PQ were associated with additional substantial reductions in gametocyte carriage. Administration of a PQ dose of 0.25 mg/kg in patients treated with AL reduced risk of gametocytemia on day 7 to 26.0%  and on day 14 to 7.6%  compared to 37.1%  and 18.2%  in patients treated with DP, respectively.A fractional polynomial model was used to estimate the probability of gametocyte carriage on days 7 and 14 for 1543 individuals receiving different PQ doses with AL or DP . Whilst P < .001, adjusted for covariates in the main analysis; P = .164, adjusted for covariates in the main analysis; The risk for gametocyte carriage was significantly higher on day 7 in patients treated with PQ on day 2 or 3 compared to patients treated with PQ on day 0 . The corresponding values on day 14 were 0.5%  in PQ-treated individuals and 9.6%  in individuals who did not receive PQ .Administration of PQ also reduced gametocyte density in those positive on days 7 or 14. Expressed as a proportion of the baseline gametocyte density, gametocyte densities reached median values of 2.0%  relative to baseline by day 7 in PQ-treated individuals compared to 29.8%  in individuals who did not receive PQ , the number of noninfectious feeds ranged from 37.8% to 67.9% (P < .001) between studies, with the lowest proportion observed in study 6 (AL/AL + PQ). This study had the lowest baseline gametocytes levels; 79.0% of patients had fewer than 50 gametocytes/µL compared to 24.7% and 42.5% in the other 2 studies.Among 316 feeding experiments conducted prior to treatment on participants with baseline gametocytemia, 186 (58.9%) infected at least 1 mosquito, with a median of 13.9%  of mosquitoes infected . While tIn patients with confirmed gametocytemia at baseline and at the time of sampling post treatment, 13.2% of feeds (36/272) of those treated with PQ infected at least 1 mosquito, compared to 35.6% (63/177) of non-PQ–treated patients sampled at the same timepoints . There wP < .001 for a participant infecting at least 1 mosquito and 10.36; 95% CI, 4.67–22.98; P < .001 for a mosquito becoming infected) and not statistically different from higher doses (0.4–0.5 mg/kg) . With the exception of those treated with AL, the odds did not decrease significantly over time for any of the schizontocidal drugs. A PQ dose of 0.25 mg/kg decreased the risk of infecting at least 1 mosquito practically to zero by day 3  and significantly decreased following PQ treatment . The redby day 3 .Methodological factors potentially contributing to the risk bias and attrition bias are presented in The only eligible study for which data were not available for this meta-analysis  presenteThis IPD meta-analysis estimated the effect of PQ as a single dose (ranging from 0.0625 to 0.75 mg/kg) on the transmission potential of falciparum malaria infections, when coadministered with schizonticidal drugs. Our findings confirm the gametocyte clearing and sterilizing effects of single-dose PQ and indicate that both the PQ and the schizonticidal partner drug are important determinants of gametocyte clearance and transmission potential. Regardless of the schizonticidal partner drug, mosquito infections were rarely observed 1 week after administration of PQ; however, only 3 of the 14 studies contributed data to this analysis.P. falciparum, PQ is unique in its ability to clear mature gametocytes persisting after ACT treatment. Because the impact of ACTs is largely restricted to immature, developing gametocytes [Among currently licensed antimalarials for etocytes , only a etocytes . In the etocytes  and tranetocytes , rather P = .202). For individuals receiving DP, the average gametocyte prevalence reduction for 0.25 mg/kg PQ was only to 39% on day 7 post treatment but higher PQ doses accelerated gametocyte clearance , and a 0.40-mg/kg PQ dose coadministered with DP achieves a similar effect to a 0.25-mg/kg dose coadministered with AL.Gametocyte kinetics in patients who presented with peripheral gametocytemia were strongly dependent on the schizontocidal treatment administered. Non-ACTs leave gametocytes largely unaffected, with gametocyte kinetics resembling a natural decay, while ACTs are only effective against early gametocytes , 20. AlsHowever, gametocyte sterilization may precede gametocyte clearance , 27. In Use scenarios for single-dose PQ include elimination settings and areas threatened by drug resistance . The finP. vivax [While CYP2D6 activity is essential for the generation of metabolites implicated in hypnozoite-clearance in P. vivax , 36, lesP. vivax . A shortP. vivax .This study also highlights SPAQ’s poor ability to clear gametocytes with a considerably higher gametocyte prevalence on day 7 post initiation of treatment compared to DP or AL . SeasonaP. falciparum malaria. Gametocyte carriage and transmission after PQ treatment depend on the schizonticidal drug that PQ is combined with, and PQ doses higher than 0.25 mg/kg may accelerate gametocyte clearance. However, this WHO-recommended dose effectively achieves near-complete reductions in mosquito infections regardless of ACT. Additional clinical trials are necessary to quantify the effect of PQ use at community level; that is, to determine whether the effect of PQ observed in mosquito feeding assays leads to detectable changes in community-wide transmission levels when the drug is systematically used in clusters of transmission.Our analysis, based on IPD from clinical trials that were primarily conducted in Africa, supports the use of PQ as a potent gametocytocide and transmission-blocking tool for The Journal of Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.Supplementary materials are available at jiaa498_suppl_Supplementary_Table_1Click here for additional data file.jiaa498_suppl_Supplementary_Table_2Click here for additional data file.jiaa498_suppl_Supplementary_Table_3Click here for additional data file.jiaa498_suppl_Supplementary_Table_4Click here for additional data file.jiaa498_suppl_Supplementary_Table_5Click here for additional data file.jiaa498_suppl_Supplementary_Figure_1Click here for additional data file.jiaa498_suppl_Supplementary_Figure_2Click here for additional data file.jiaa498_suppl_Supplementary_MethodsClick here for additional data file.


Gastrointestinal helminth parasite infection is a major influencing factor against the profitability of working equines all over the world.  A cross-sectional study was conducted to determine the prevalence of gastrointestinal tract (GI) helminths and assess the associated risk factors in donkeys and horses in the Hawassa district. A total of 214 fecal samples were collected from randomly selected equines (112 donkeys and 102 horses) and examined for the presence of eggs of GI helminths using standard coprological techniques. Strongyle species 120 (56.1%), Strongyloides westeri 76 (35.5%), Parascaris equorum 54 (25.2%), Anoplocephala perfoliata 34 (15.8%), Oxyuris equi 20 (9.3%), Fasciola hepatica 18 (8.8%), Gastrodiscus species 12 (5.6%), and Dictyocaulus arnfieldi 4 (1.8%). There was a strong association between the prevalence of GI helminths and factors such as the species of equine, body condition scores, and feed type (p < 0.05). However, no significant association (p > 0.05) was observed between the prevalence of GI helminths and putative risk factors such as age, sex, housing, and water source. The coproculture performed on 30 pooled fecal samples revealed that Cyathostomes species, Strongylus vulgaris, and Strongylus edentatus were the major helminth parasites of donkeys and horses.  According to the current study, the prevalence of GI helminths in equine was 78.5% (168/214) and the highest prevalence was reported in donkeys 92% (103/112) as compared to horses 63% (65/102). Out of 168 positive samples, the different species of parasites were identified, namely,  The frequency of gastrointestinal helminths in equine species was high, especially in donkeys. Hence, strategic deworming using broad-spectrum antihelminthic drugs and a rotational grazing program should be implemented to control and prevent the diseases. Equus asinus) and horses  are among the early domesticated equines that have been around as long as 3000 years ago [Donkeys , feeding, and water were considered. The study includes horses and donkeys of all age groups and both sexes, kept under extensive management systems. The age of the selected horse and donkeys was determined from birth records and dentition characteristics  accordinN = required sample size, Pexp = expected prevalence, d = absolute precision, and Z = 1.96 at 95% level of confidence. Thus, a total of 214 cattle were included in the current study.The sample size required for this study was determined according to the work of Thrusfield . There wFecal samples were collected directly from the rectum or sometimes from freshly passed feces using plastic gloves in clean plastic bags. Along with sampling, date, name, identification number, age, sex, BCs, feed type, housing condition, and water source were recorded. Then, all fecal samples were transported to the Hawassa University parasitology laboratory for further fecal examination from the selected site by using iceboxes and analyzed in the regional laboratory. Fecal samples were examined using standard parasitological techniques  and examined using 10x and sometimes 40x magnification power .The larvae were then identified based on the shape and number of gut cells, relative size, and shape of the larvae's tail. The floatation fluid used in this study was a supersaturated solution of sodium chloride (NaCl) salt prepared in the laboratory according to the procedures given by Zajac and Conboy . Moreovechi-square (X2) test. For all analysis, a p value less than 0.05 was considered as significant.The collected data from the field were entered into a Microsoft Excel 2016 spreadsheet and analyzed using the STATA version 13 software program. The prevalence was calculated as the number of animals having parasites, divided by the total number of animals examined. The association between the risk factors and the outcome variables was assessed using the The overall prevalence of helminth parasites of equine in the study area was found to be 78.5% (168/214) with a prevalence of 91.9% (103/112) and 63.73% (65/102) in donkeys and horses, respectively .Strongyle species 120 (56.1%), Parascaris equorum 54 (25.2%), Strongyloides westeri 76 (35.5%), Oxyuris equi 20 (9.3%), Dictyocaulus arnfieldi 4 (1.8%), Anoplocephala perfoliate, 34 (15.8%), Fasciola hepatica 18 (8.8%), and Gastrodiscus species 12 (5.6%)  .Strongyle species, Strongyloides westeri, and Parascaris equorum was 66%, 50%, and 34.8%, respectively, while in horses, the prevalence of Strongyle species, Strongyle westeri, and Anoplocephala perfoliata was found to be 45.1%, 19.6%, and 15.7%, respectively. In both donkeys and horses, Strongyle species were found as the most prevalent GI helminth parasites in the study area. However, Dictyocaulus arnfieldi were the least prevalent parasites in donkeys with no observation of this parasite in horses during the study period  of the prevalence of GI parasites with species of animal, body condition score, and feed type. However, age, sex, housing, and water have no significant association (p > 0.05) with the prevalence of GI parasites  and Cyathostomins species (36.6%) were recorded in a higher proportion in horses than in donkeys, whereas a higher proportion of Strongylus edentatus (13.3%) was recovered from donkeys than horses  with the prevalence of GI parasites and feed which was in agreement with the work of Mezgebu et al. [The prevalence of GI helminths reported in the same study area by Ibrahim et al.  and Berhu et al. .In this study, a relatively higher prevalence of gastrointestinal parasites was recorded in donkeys 97.1%) than horses (81%). This was comparable with the previous finding of Debere et al. , who rep.1% than Strongyle species in horses was 45.1% in the current study which was lower than the previous reports described by Mezgebu et al. [The prevalence of u et al.  who repou et al.  who repoStrongyle-type infestation in donkeys was 66.07%. This result disagreed with studies conducted in different areas with 87.8% by Mezgebu et al. [The prevalence of u et al.  in Gondau et al.  in Hawasu et al.  in Bishou et al.  in Jigjiu et al.  in Konyau et al.  in AlageStrongyloides westeri in the horses was 19.6% which was in agreement with the work of Ibrahim et al. [Strongyloides westeri in the study area. Its prevalence in donkeys was 50.0% which is higher than in the report of Uslu and Guçlu [The current prevalence of m et al.  who repom et al.  in Konyand Guçlu  in Konyand Guçlu  in TentaParascaris in horse under this study was 14.7% which was lower than in the reports of Berhanu et al. [Parascaris in the present study was higher than in the previous report by Tesfu et al. (2014) in Hawassa Town, Uslu and Guçlu [The prevalence of u et al.  (55.8%) u et al.  in and au et al.  in Bishond Guçlu  in Konyand Guçlu  in MekelParascaris was found to be 34.8% which was higher than the prevalence reported by Getahun and Kassa [In donkeys, the prevalence of nd Kassa  (11.2%) nd Kassa  in and and Kassa  in Hawasnd Kassa  in Bishond Kassa  in Konyand Kassa , Ibrahimnd Kassa , Abdulahnd Kassa , and Meznd Kassa  who reprOxyuris equi in horses was 9.8% which was nearly in agreement with the prevalence reported by Uslu and Guçlu [Oxyuris equi in donkeys were 8.9%, which showed a significantly higher prevalence as compared with other studies mentioned by Mezgebu et al. [The current prevalence of nd Guçlu  (8.8%) ind Guçlu  in Bishond Guçlu  in Mekelnd Guçlu  in and and Guçlu  in Gondand Guçlu  in Konyau et al.  in and au et al.  in Bishou et al.  in Konyau et al.  in TentaThe current prevalence of Fasciolosis in horses was 13.7%, which disagreed with the work of Ayana et al.  who repoAnoplocephala perfoliata in horses was 15.7% which is higher than the prevalence reported in 2.7% by Uslu and Guçlu [Anoplocephala perfoliata in donkeys was 16.1% which showed a higher infestation rate as compared with 6.2% by Uslu and Guçlu [The prevalence of nd Guçlu , 2% by Bnd Guçlu , and 1.6nd Guçlu . Also, tnd Guçlu , 2.6% bynd Guçlu , and 2.7nd Guçlu .Dictyocaulus arnfieldi was not observed in the horse. However, its prevalence in donkeys was 3.6% which agreed with the previous report by Ibrahim et al. [In the present study, m et al. , who repGastrodiscus species was 6.8% and 4.5% in horses and donkeys, respectively. These results were higher than Mezgebu et al. [The current prevalence of u et al.  who repou et al.  in HoletCyathostomins species was highly prevalent than S. vulgaris and S. edentatus with a prevalence of 43.3% and 63.3%; 26.6% and 36.6%; and 13.3% and 10% in donkeys and horses, respectively. This higher prevalence of cyathostomins species in the present studies was in agreement with Uslu and Guçlu [From the coproculture study, the present study revealed that nd Guçlu .p < 0.05) with the occurrence of the disease. Strongyle species (56.1%), Parascaris equorum (25.2%), Strongyloides westeri (35.5%), Oxyuris equi (9.3%), Dictyocaulus arnfieldi (1.8%), Anoplocephala perfoliate, (15.8%), Fasciola hepatica (8.8%), and Gastrodiscus species (5.6%) were the most dominant gastrointestinal parasites affecting horse and donkeys in the study area. The coproculture investigation revealed that Strongylus vulgaris (36.6%) and Cyathostomins species (36.6%) were recorded commonly in horses as compared to donkeys, whereas a higher proportion of Strongylus edentatus (13.3%) was recovered from donkey than horses.Internal parasites are important health problems of equines in the study area with an overall prevalence of 78.5%, especially the highest in donkeys with 92% followed by horses (63%). Factors such as species, body condition, and feed type were strongly associated (In conclusion, in order to minimize losses attributed to the equine internal parasites in the area, equine owners should be informed of the economic importance and methods of control and prevention of helminths of equines through management improvements. Furthermore, regular and strategic deworming programs with efficacious anthelmintics should be carried out regularly.