P < 0.01), and mean CMT decreased significantly in each group (both P < 0.01). Thirteen eyes underwent additional vitrectomy, six eyes developed neovascular glaucoma, six eyes received intravitreal anti-VEGF injection, and thirteen eyes received subtenon triamcinolone acetonide injection. Multiple linear regression analysis showed that baseline VA and CMT in the TME group and kidney function in the nTME group were the predictable factors of the 12-month postoperative VA. Twenty-five-gauge vitrectomy effectively improved VA and macular structure both in TME and nTME groups. Baseline VA, CMT, and kidney function are important factors affecting postoperative VA.The benefit of pars plana vitrectomy with internal limiting membrane peeling for tractional macular edema and diffuse nontractional macular edema in diabetic retinopathy has been reported. Although these studies had included various stages, use of conventional 20-gauge vitrectomy system, small number of cases, single-center study, and lack of retinal structure measurements were limitations. We compared one-year outcomes of 25-gauge vitrectomy for refractory diabetic macular edema with or without the tractional proliferative membrane in proliferative diabetic retinopathy (PDR) eyes and examined the prognostic factors for postoperative visual acuity. A total of consecutive 116 PDR eyes of 116 patients that underwent 25-gauge vitrectomy for tractional macular edema (TME group: 56 eyes) or nontractional macular edema (nTME group: 60 eyes) at six centers were retrospectively reviewed. Visual acuity (VA), central macular thickness (CMT), complications, and postoperative treatments before and 12 months after vitrectomy were compared. Mean VA improved significantly in each group (both  Diabetic macular edema (DME) is a common cause of visual loss in diabetic retinopathy (DR) and is a complication in any stages of DR including proliferative diabetic retinopathy (PDR) . The curCompared to the 20-gauge vitrectomy system, microincision transconjunctival sutureless vitrectomy systems decrease surgical invasion, shorten the operating time and duration of hospitalization, and lower the incidence of intra- and postoperative complications –11. VitrAlthough previous studies have shown the benefit of vitrectomy for TME or nTME in diabetic retinopathy , 19, theThis study was an observational case series of 116 eyes of 116 consecutive participants with type I (4 participants) or II (112 participants) diabetic mellitus who underwent primary 25-gauge vitrectomy for PDR with DME in six centers  between April 2010 and March 2016. The study was conducted according to the tenets of the Declaration of Helsinki and was approved by institutional review board of each of the six hospitals. Inclusion criteria were as follows: (1) All participants had intravenous fluorescein angiograms before vitrectomy or after vitrectomy to confirm the diagnosis of PDR by two ophthalmologists. In cases with vitreous hemorrhage (VH) which obscures complete fundus observation before vitrectomy, two ophthalmologists confirmed the diagnosis of PDR by fundus observation and fluorescein angiograms after vitrectomy. (2) All participants were candidates for vitrectomy and signed a preoperative informed written consent form for the surgical procedure. (3) Participants with follow-up periods more than 12 months. Exclusion criteria were as follows: (1) participants with a follow-up period of less than 12 months, (2) other causes of proliferative vitreoretinal disease, (3) central retinal ischemia detected by intravenous fluorescein angiograms, (4) having a past history of vitrectomy, (5) having a past history of other retinal disease such as retinal vein occlusion and age-related macular degeneration, and (6) having a past history of any type of glaucoma.All eyes were classified into TME group and nTME group. TME contained the proliferative membrane around the macula which attached the fovea and macular edema, while nTME lacked the proliferative membrane attaching to the fovea and macular edema. This classification was decided by at least 2 retinal specialists in each center at the primary vitrectomy based on preoperative fundus examination, color photographs, spectral domain-optical coherence tomography (SD-OCT) findings, and ultrasonography or intraoperative findings as described previously , 21.G followed by removal. Eyes with insufficient previous panretinal photocoagulation received additional intraoperative panretinal photocoagulation. No eye had received intravitreal anti-VEGF injection or intravitreal/subtenon triamcinolone acetonide injection at the end of vitrectomy. After vitrectomy, topical antibiotic and anti-inflammatory agents were administered 4 times daily for 1 month, and postoperative additional treatments, i.e., revitrectomy, intravitreal anti-VEGF injection, subtenon triamcinolone acetonide (STTA) injection, and cataract surgery, were performed by the clinician's decision, but no eye had received intravitreal triamcinolone acetonide injection.All eyes underwent 25-gauge vitrectomy using a wide-angle viewing system. In brief, the posterior vitreous was separated from the retina by active aspiration with the vitrectomy probe, and all visible vitreous strands that adhered to the retina were removed. Intravitreal triamcinolone acetonide  was systematically used in all cases to facilitate visualization and removal of the adherent posterior cortical vitreous. ILMP was systematically performed by staining the ILM with brilliant blue At each visit, the patients underwent a complete ophthalmologic examination including best-corrected visual acuity, refractive measurement, SD-OCT, intraocular pressure measurement, slit-lamp examination, and dilated fundus examination (using contact and noncontact fundus lenses). Visual acuity was measured using the standard Japanese decimal visual acuity chart, and the values were converted to logarithm of the minimum angle of resolution (LogMAR) units for data analysis, as described previously . IntraocBaseline general conditions , systemic hypertension, and anticoagulant therapy), baseline ocular conditions , surgical procedures , postoperative complications , and postoperative additional treatments  were evaluated. HbA1c is expressed in the National Glycohemoglobin Standardization Program (NGSP) unit . HyperteU test and chi-square test were used to compare the data between the two groups, and repeated measures ANOVA and the Bonferroni correction were used to compare the changes in LogMAR and CMT in the group. Multiple linear regression analysis was used to detect the correlation between the change in LogMAR and other factors. A P value less than 0.05 was considered significant.Results are expressed as mean ± standard deviation with range [low–high] for continuous variables. The Mann–Whitey Baseline characteristics, surgical procedures, and postoperative complications and additional treatments in TME and nTME groups are shown in P < 0.001) but no significant differences in baseline general conditions between two groups. In surgical procedures, combined cataract surgery was performed more frequently in the TME group than that in the nTME group (P < 0.001). However, the eyes with intraocular lens (IOL) were 50 eyes in the TME group and 47 eyes in the nTME group at 12 months after vitrectomy, and statistical difference was not observed between the two groups. In postoperative complications, 13 eyes (8 eyes in the TME group and 5 eyes in the nTME group) underwent revitrectomy, and 5 eyes (1 eye in the TME group and 4 eyes in the nTME group) developed postoperative NVG. In additional treatment, 2 eyes (3 months and 10 months after vitrectomy) received intravitreal anti-VEGF injection and 10 eyes  received STTA injection in the TME group, and 4 eyes  received intravitreal anti-VEGF injection and 3 eyes at 1 month after vitrectomy received STTA injections in the nTME group.The TME group consisted of 56 eyes of 56 patients , and the nTME group comprised 60 eyes of 60 patients . There were significant differences in vitreous hemorrhage (P < 0.001) at 6 months, and 0.69 ± 0.78 [3.0 to −0.08] and 0.36 ± 0.41 [1.5 to −0.08] (both P < 0.001) at 12 months .The mean visual improvement in the TME group and nTME group was 0.39 LogMAR (corresponding to a mean increase of 3.9 lines) and 0.78 LogMAR (mean increase of 7.8 lines), respectively, from baseline to 6 months, −0.03 LogMAR (mean decrease of 0 lines) and 0.12 LogMAR (mean increase of 1.2 lines) from 6 months to 12 months, and 0.36 LogMAR (mean decrease of 3.6 lines) and 0.90 LogMAR (mean increase of 9.0 lines) from baseline to 12 months, respectively . In the P=0.058). Subsequently, we evaluated the differences between eyes with and without visual improvement in TME and nTME groups , CMT (P=0.005), and VH (P=0.019) between improved and nonimproved eyes. In the nTME group, there were significant differences in baseline LogMAR (P=0.001) and VH (P=0.037). We then evaluated the differences between LogMAR at 12 months better and worse than 1.0  had better baseline LogMAR (P=0.002) than eyes with LogMAR worse than 1.0 (n = 16). In the nTME group, eyes with LogMAR better than 1.0 (n = 51) were younger (P=0.0017), had shorter diabetic duration (P = 0.0069), and had better baseline LogMAR (P=0.039) than eyes with LogMAR worse than 1.0 (n = 9).In the TME group, eyes with LogMAR better than 1.0  at 6 months and 259 ± 109 [195–610] and 277 ± 110 μm [101–700] (both P < 0.01) at 12 months : 0.24–0.75) and baseline CMT  and negative correlation between VH  were observed in the TME group, while a positive correlation with diabetic duration  and a negative correlation with eGFR  were observed in the nTME group (We conducted multiple linear regression analyses to examine the relationship between LogMAR at 12 months and baseline LogMAR or VH in the TME group and baseline LogMAR, diabetic duration, VH, and eGFR in the nTME group, which might affect postoperative LogMAR in the TME group and nTME group Tables  and age ME group .The present study found no significant differences in the improvement of LogMAR and reduction of CMT after microincision transconjunctival sutureless vitrectomy with ILMP between TME and nTME in the eyes with PDR. Approximately 40% of TME patients and 80% of nTME patients had visual gain of more than 2 lines at 12 months. Furthermore, no significant differences in surgical complications were found between TME and nTME. Finally, baseline LogMAR and CMT in TME and baseline LogMAR and kidney function in nTME were identified as independent predictive factors of the final LogMAR.http://DRCR.net prospective study on vitrectomy outcomes in the eyes with diabetic macular edema and vitreomacular traction reported significant visual improvement in 38% and significant visual deterioration in 22% of the subjects [http://DRCR.net prospective study [The effectiveness of vitrectomy for tractional DME was demonstrated by Lewis et al.  in 1992 subjects . In the ve study . Howeverve study , 24.In clinical situation, there is a good deal of evidence suggesting that vitrectomy effectively restores retinal function and significantly decreases macular edema. Lewis et al. reported that vitrectomy was effective in the eyes with macular edema associated with a thickened and taut posterior hyaloid membrane . AlthougVitrectomy for PDR is associated with certain complications, including postoperative VH, cataracts progression, IRT, retinal detachment, and NVG , 13, 19.Renal dysfunction is associated with an increased likelihood of worsening diabetic retinopathy . A retroIn the surgical procedure, all eyes had received intravitreal triamcinolone injection and many eyes had additional retinal photocoagulation. Intravitreal triamcinolone and retinal photocoagulation had some effects for the postoperative retinal structure and even visual outcomes in short term and would not continue after 6 months. Additional anti-VEGF and STTA injections were performed in 19 eyes. In the two groups, anti-VEGFs were performed at 1 month, 3 months, 6 months, and 10 months after vitrectomy. STTA injections were performed at 1 month, 3 months, and 6 months. In general, these treatments present immediate effects and do not continue for a long time. However, it is possible that the efficacy might affect the visual and anatomical outcomes at 6 months or 12 months in some cases.This study has several limitations. The major limitation is the retrospective multicenter comparative study without any control group although all surgical procedures were performed under similar conditions. Baseline factors which affect postoperative LogMAR, such as lens status, anti-VEGF and STTA injections, and VH, were evaluated although macular degeneration or optic nerve atrophy could not be standardized or excluded. A second limitation is that only Japanese subjects were studied and both type 1 and type 2 diabetes mellitus were included. Finally, the absence of difference between the two groups may be simply attributable to the lack of statistical power in this study or to selection bias.This study confirmed the functional and anatomical efficacy of vitrectomy for both tractional and nontractional DME in PDR eyes, without severe surgical complications. The real-world outcomes obtained from this multicenter study are more reliable than previous single-center studies. The high and increasing prevalence of DME and the existence of nonresponders to anti-VEGF therapy require consideration of alternative therapies such as vitrectomy that may improve diabetic patient care.


Objective: Cervical bone fractures describe a predominant trauma in the elderly. With demographic change, prone patient positions might create further stress on personnel resources. Therefore, the aim of this study was to conduct an age-related analysis of pre- and intraoperative process times in patients with cervical fractures.Methods: We reviewed all schedules with cervical spine surgery performed at a tertiary hospital. Two different operative patient positions were specified: prone and supine. We retrospectively analysed three study groups: comparison group (group 1: ≤59 years of age), old patients (group 2: 60–79 years), and very old patients (group 3: ≥80 years). We recorded date and kind of surgery, biometric data, and process times by screening recordings of internal software programs (COPRA® and SAP 710®). Group comparisons were conducted using the Kruskal-Wallis test with Dunn’s post hoc test and Bonferroni correction, Pearson’s chi-square test, and the Mann-Whitney U test, as required. Results: 330 patients  were analysed. The number of patients in the resulting age-dependent groups 1–3 were n=102, n=123, and n=105, respectively. Patients of increasing age and in supine position showed a continuous increase in the time needed for anaesthesia induction (mean between 4 and 8 minutes (p<0.05). When compared to patients in supine position, this time further increased on average by 6 minutes (p<0.05) in old but prone patients. In old and very old patients, getting a patient into a prone position was associated with a time demand between 10 and 12 minutes (p<0.01), respectively. While time for surgery age-dependently decreased in patients that were supine positioned (p<0.001), surgery time was prolonged between 34 and 104 minutes (p<0.05) in patients that were prone. Conclusion: With prone position both anaesthesia-controlled and surgical-controlled times extended in patients of increasing age. With regard to demographic change, this aspect should be considered for future revenue calculations in flat-rate remuneration systems. With a share of 25% of all lesions, cervical bone fractures are one of the most common injuries of the cervical spine. For example, odontoid fractures describe a predominant trauma in the elderly that is frequently promoted by osteoporosis and degenerate joint changes , [2], 33. As a fWhile the operating room (OR) is a cost-intensive environment, effective scheduling of the surgical suite has already become an essential prerequisite for efficient OR management . With de® and SAP 710®). All data were transferred into electronic data  for statistical analysis. This retrospective study has been accepted by the local ethics committee (235-13-26082013). We reviewed all schedules with cervical spine surgery at the University Hospital Leipzig from 2002 to 2012. Two different operative patient positions were specified: prone (posterior stabilization) and supine (anterior stabilization). We recorded the patient’s age, date of surgery, biometric data, and process times by screening recordings of internal software programs  was performed. If these injuries were associated with arthrosis of the C1/2-joint and/or a fracture of the atlas, a transarticular atlantoaxial fixation with odontoid fusion (TAFOF) was made. Injuries with sub C2 diagnosis associated with disc injuries were mainly treated via anterior cervical decompression and fusion (ACDF). A prone patient position became necessary in cases of atypical odontoid fractures, dens dislocations >2 mm, or a pseudarthrosis of the dens, in order to facilitate a posterior stabilization of the C1/2-joint. In addition, all injuries with neurological deficits required a posterior stabilization and decompression in a prone position. We divided all patients by their age at the time of surgery into three groups: comparison group (group 1: ≤59 years), old patients (group 2: 60–79 years), and very old patients (group 3: ≥80 years). The process times correspond to those defined in the glossary of perioperative process times of the German Society of Anaesthesiology and Intensive Care Medicine . Comparisons between age groups were conducted using the Kruskal-Wallis test with Dunn’s post hoc test and Bonferroni correction and Pearson’s chi-square test. The Mann-Whitney U test was used for a comparison between prone and supine patient position. Correlation analysis was performed using the Spearman’s rank correlation coefficient. We displayed data as an arithmetic mean and standard deviation. Statistical significance was accepted at two-sided p-values <0.05.Statistical analysis was computer based, using SPSSIn total, 330 patients  were analysed. The number of patients in the resulting age-dependent groups 1–3 were n=102, n=123, and n=105, respectively. Of the patients, 24% were in prone position (n=79). Many more cervical spine operations were performed in supine position , and the number increased with increase in age . Controls and old patients comprised mostly male patients (p<0.001) that had suffered an accident in the household (52%) or due to road traffic (28%). In contrast, very old patients were mostly female (p<0.001) and threatened by a low-velocity fall (63%). Table 2 Values of respective process times for each age-dependent group are presented in Table 3 The time needed for anaesthesia induction (delta 2) increased with increase in age. Between group 1 and old patients, induction time increased on average by 5 minutes (p=0.029). Between group 1 and very old patients (group 3), this time increased on average by 7 minutes  shortened with increase in age. Time for surgery decreased between group 1 and old patients (group 2) on average by 22 minutes (p=0.019). Compared with group 1, this time decreased on average by 49 minutes (p<0.001) in very old patients  in relation to the operating time was 35%, 42%, and 49%, respectively. Concerning both patients’ age and positioning (supine versus prone), the resulting process times are pictured in Figure 2 Getting a patient into a prone position was associated with a prolonged process time that lasted from anaesthetists’ release of the patient for surgery until the start of surgery (delta 4). In prone patients, this process was prolonged and lasted on average 12 minutes more (p<0.01) in old and 10 minutes (p<0.01) more in very old patients, respectively Table 4 .With increasing age, time for surgery (delta 5) continuously decreased in patients that were treated in a supine position (p<0.001). In contrast, patients that were prone showed an increase of delta 5 in an age-dependent manner (p<0.001). When compared to supine position and group-by-group, prone patients showed a prolonged surgical time between 34 and 104 minutes on average  physical status. An associated ASA class IV triples the anaesthesia preparation time compared with ASA physical status class I , 7]. Th. Th7]. TWe hypothesized that shifting an anesthetized patient into a prone position is a time-consuming process. Indeed, getting a patient into a prone position required about ten minutes. In those cases, time for surgery additionally increased, with total case time markedly prolonged. On the other hand, our results show that the older the patients were, the more often they were operated on in a supine position. Thus, octogenarians mostly suffered odontoid fractures, which were treated by an anterior screw fixation or transarticular atlantoaxial fixation. Both techniques, performed in supine patient position, were associated with an increase in anaesthesia-controlled time, but the time for surgery markedly decreased. In consequence, an extension of an anaesthesia-controlled time was more than compensated for by a shortened time for surgery. In conclusion, when older patients with a fractured cervical spine were treated in a prone position, both anaesthesia-controlled and surgical-controlled times were markedly prolonged. With regard to demographic change, this aspect should be considered for future revenue calculations in flat-rate remuneration systems.The authors declare that they have no competing interests.This study was approved by the local ethics committee (235-13-26082013).


Background: Dexmedetomidine possesses sedative, sympatholytic, and opioid-sparing properties, but its impact on postoperative gastrointestinal function is controversial.Methods: This single-center, prospective, randomized study compared low-dose dexmedetomidine and placebo on gastrointestinal function recovery and inflammation after posterior lumbar spinal fusion. Sixty-six patients were randomized into two groups and received normal saline (control group) or dexmedetomidine (DEX group) during posterior lumbar fusion. Blood was taken at five timepoints to measure lipopolysaccharides, tumor necrosis factor-α, and C-reactive protein. The primary outcome was duration to first flatus. The secondary outcomes were inflammatory mediators and determination of correlations between perioperative factors and duration to first flatus.Results: Patients in DEX group showed significantly lower duration to first flatus  and overall sufentanil consumption  than controls. Lipopolysaccharides, tumor necrosis factor-α, and C-reactive protein did not differ between the groups at any timepoint . Multiple linear regression modeling assessed the ability of independent variables to predict variance in duration to first flatus . In the model, age , gender , BMI , operative segments , and overall sufentanil consumption  contributed significantly.Conclusions: Thus, low-dose dexmedetomidine accelerates gastrointestinal function recovery after lumbar spinal fusion. The effect may be partially produced by opioid-sparing effects rather than inhibition of inflammation.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR1800018127. Patients undergoing lumber spinal surgery usually encounter postoperative transient gastrointestinal (GI) dysfunction due to prolonged bed rest. The incidence of postoperative ileus was 26.0 per 1,000  in poste2-adrenoreceptor agonist widely used as an anesthetic adjuvant during surgery  is a potent and highly selective α surgery . DEX als surgery  and is s surgery . Chen etin vitro , animal in vitro  and healin vitro . The mecoceptors ; on the istalsis . The inhistalsis . This stThis single center trial has a prospective, randomized parallel-group design. The present study was conducted at Xuan Wu Hospital, Capital Medical University  from September 1, 2018, to March 1, 2019. The hospital’s Ethics Committee approved the study protocol (2017–076), which was performed in accordance with the Declaration of Helsinki. After approval, this study was registered in the Chinese Clinical Trial Registry  and adhered to CONSORT guidelines. Verbal and written informed consents were obtained from all the included patients.2-adrenergic receptor agonist, difficulty in communication, abnormal liver or renal function, and bowel disease .Patients with lumbar disk herniation or lumbar spondylolisthesis undergoing elective lumber spinal surgery were enrolled into this study. The type of surgery was posterior lumbar discectomy + pedicle screw fixation +intertransverse fusion. The inclusion criteria were an American Society of Anesthesiologists physical status below 4 and patients aged 18 years or older. The exclusion criteria included patient refusal to participate at any time, preoperative use of opioid, bradycardia (heart rate < 50 bpm), heart block greater than the first degree, preoperative use of antihypertensive drugs containing clonidine or an αhttps://tools.medsci.cn/rand)—generated codes stored in sequentially numbered and sealed envelopes. The study agents  were prepared in identical 50-ml syringes by a research nurse who was blinded to group assignments. The randomization code was broken only after patient enrollment and follow-up had ended. All surgeons, patients, attending anesthesiologists, nurses, and follow-up anesthesiologists were blinded to group assignments.The included patients were randomized into two groups with an allocation ratio of 1:1 and either received normal saline (control group) or low-dose DEX (DEX group) during surgery. Randomization was based on online randomization software  to maintain an end-tidal CO2 between 30 and 35 mm Hg. Total intravenous anesthesia was maintained with continuous infusion of remifentanil (0.3–0.4 µg/kg/min), propofol (3–6 mg/kg/h), and cisatracurium (1–2 µg/kg/min). The propofol infusion rate was hand-titrated to maintain a bispectral index value between 40 and 60. Additional sufentanil was added in 10-µg increments at the skin incision as needed as well as 30 min before surgical suture.The anesthesia management protocol was standardized among the groups. All patients fasted for 12 h and were given soapsuds enemas the night before surgery. Heart rate, invasive blood pressure, pulse oxygen saturation, nasopharyngeal temperature, end-tidal carbon dioxide level, and bispectral index  were routinely monitored. Goal-directed fluid therapy was used intraoperatively to maintain pulse pressure variation below 13%. The maintenance fluid infusion rate was set at 1–2 ml/kg/h. Anesthesia was induced with etomidate (0.2–0.3 mg/kg), sufentanil (0.2–0.3 µg/kg), and rocuronium (0.6–0.8 mg/kg). Volume-controlled ventilation was performed with an oxygen-air mixture (fraction of inspired ODEX group patients were given dexmedetomidine (4 μg/ml) continuously after turning to the prone position; the loading dose was 0.5 μg/kg for 15 min and was then maintained at a rate of 0.1 μg/kg/h until 30 min before skin suture. The control group underwent the same procedure but received saline instead.The day before surgery, all patients were instructed on the use of a 10-point numeric rating scale to assess their pain intensity . Postoperative patient-controlled intravenous analgesia was performed with sufentanil (1.5 μg/kg). All patients received a basal dose of (0.015 μg/kg/h) and PCA (0.03 μg/kg). The interval time was set at 10 min, and patient-controlled intravenous analgesia was maintained up to 72 h following surgery to make sure all patient numeric rating scale scores were below 3.0), at the end of surgery (T1), and 24 h (T2), 48 h (T3), and 72 h (T4) after surgery. All blood samples without anticoagulation were centrifuged at 3000 rpm for 15 min to collect serum, which was frozen at −80°C. Enzyme-linked immunosorbent assay kits were used to measure serum concentrations of the inflammatory mediators C-reactive protein , tumor necrosis factor-α , and lipopolysaccharides  according to the manufacturers’ instructions. All samples were analyzed at a dilution resulting in concentrations within the range of the standard curve.Blood samples (3 ml each) were taken from a peripheral vein at the following timepoints: before induction , before intervention, immediately after loading dose, and at the end of surgery. The overall consumption of DEX and narcotics, surgical indices, including operative segments, anesthesia duration, surgical duration, blood loss, urine output, and fluid infusion amount, were recorded. Duration to first flatus and needs for blind enema were recorded during follow-up.0), at the end of surgery (T1), and 24 h (T2), 48 h (T3), and 72 h (T4) after surgery.The primary outcome of the present study was duration to first flatus, which was self-reported by patients and recorded by a follow-up anesthesiologist who was blinded to group assignments during follow-up. The secondary outcomes were inflammatory mediators and determination of any correlations between perioperative factors and duration to first flatus. Inflammatory mediators were assessed at the following timepoints: before induction , the duration to first flatus was 21.1 h [5.8 h] in the DEX group and 25.6 h [8.3 h] in the control group. This meant that a sample size of at least 33 was needed in each group to have a power of 95% to detect differences of 10% or more between the groups. Therefore, a total of 90 patients were initially recruited in the present study to compensate for any exclusion and ensure a minimum sample size of at least 33 patients per group.According to the results of a preliminary study  of rank data and non-normally distributed quantitative variables are also presented, with intergroup comparisons made with the nonparametric Mann–Whitney test. Qualitative variables are expressed as percentages and were compared via Chi-squared test. Multiple linear regression was performed to assess the ability of perioperative factors to predict variances in duration to first flatus. A p < 0.05 was considered statistically significant.Statistical analysis was done with SPSS software version 17.0 . All quantitative data are presented as means ± standard deviations, with intergroup comparisons made by unpaired Student’s n = 38) and control (n = 39) treatment groups. After exclusion of an additional 11 patients, data from a total of 66 patients (n = 33 per group) were included in the analysis  vs 19.58 (17.31–21.86) h; 0) serum LPS was obviously higher than the normal limit (<54.2 EU/L) in both treatment groups. While the T1–T4 LPS levels in the DEX group were all significantly lower than that at T0 , the control group levels did not begin to significantly decrease until T2 . Gender  and operative segments  were analyzed as categorical variables in the multiple linear regression analysis. In the model, age , gender , BMI , operative segments , and overall sufentanil consumption  contributed significantly  to predict variance in duration to first flatus was statistically significant  (2), thus we observed a negative association of BMI with duration to first flatus. Our results also indicated that gender and operative segments were associated with duration to first flatus. Male gender was reported to be an independent risk factor for postoperative ileus in anterior lumber interbody fusion in the elderly  . Murphy  elderly . Surgeon2-adrenoreceptor activation, which causes vasoconstriction, vasodilation, and reflex bradycardia. With a low dose of DEX, the present study found that the incidence of bradycardia in DEX group patients was even lower than in the control.Side effects of DEX are mainly restricted to hemodynamic alterations. These alterations include hypertension, bradycardia, and hypotension owing to pre- and postsynaptic αThere were several possible limitations to the present study. First, only duration to first flatus was used to evaluate recovery of GI function. Duration to first flatus was reported by patients, and it may be relatively unreliable. Although no single objective variable has yet been found to accurately predict GI function recovery, future studies should employ combined functional outcomes of normalization of food intake and bowel function to adequately define this parameter. In addition, only one low dosage of DEX was employed to investigate the relationship between inhibitions of surgical stress and enhanced GI function recovery. More doses should be used to further investigate this relationship in future.The present study revealed that administration of low-dose DEX during surgery can accelerate GI function recovery in patients undergoing lumbar spinal surgery. This effect might partially be due to DEX’s ability to reduce postoperative opioid consumption rather than attenuation of inflammatory responses. The present results provide new insights for postoperative GI function recovery, showing that age, gender, BMI, operative segments, and overall sufentanil consumption significantly correlated with duration to first flatus.All datasets generated for this study are included in the article/supplementary material.The studies involving human participants were reviewed and approved by Ethics Committee of Xuan Wu Hospital, Capital Medical University . The patients/participants provided their written informed consent to participate in this study.ML: Design and initiation of the study, patient recruitment, monitoring of processes, compilation of the CRF database, statistical analyses, composition of the first draft of the manuscript and preparation of the figures. TW: Design and initiation of the study, patient recruitment, monitoring of processes, compilation of the CRF database, statistical analyses, composition of the first draft of the manuscript and preparation of the figures. WX: Study conception and design, data acquisition and interpretation, article drafting, and critical review of the article. LZ and DY: contributed to the interpretation of the data, critical review of the article. Revision and approval the final version of the paper: all authors.This study was supported by Beijing Municipal Administration of Hospitals Incubating Program (CODE:PX2019031), Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201818) and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201706).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Allokermes galliformis  (Hemiptera: Coccomorpha: Kermesidae) is described for the first time in Colorado, United States of America. This scale insect species recently emerged as a significant pest of red oaks in Colorado through its causative role in drippy blight disease. A description and illustration of the adult male characterize its key external morphological characteristics.The adult male of  Allokermes, Eriokermes, Kermes, Nanokermes, and Olliffiella) . Nhe genus ,9,10,11,uercina) ,13. In tll, 1898 ,15. FurtAllokermes galliformis was originally described from female syntypes from Iron Mountain, (St. Francois County) Missouri [Allokermes is generally lacking with only the male of A. kingii  described [Quercus rubra L.) has allowed us to provide a detailed morphological description of the adult male of A. galliformis.Missouri . MorpholMissouri ,10. AlthMissouri , the aduescribed . The abuAllokemes galliformis females feeding on red oak trees in Boulder, Colorado, USA, was determined by the morphological characteristics of pre-reproductive adults [Allokermes gillettei (Cockerell) can also be found in the region, but this species is host specific to gambel oak (Q. gambelii) [A. galliformis females, coupled with the red oak host plant association, led to the male species determination of Allokermes galliformis.The identification of e adults . Allokerambelii) . In thisSpecimens were stored in 90% ethanol at 4 °C until slide mounting or scanning electron microscopy. All slide mounted specimens and additional voucher specimens preserved in 80% ethanol were deposited in the C.P. Gillette Museum of Arthropod Diversity, Colorado State University, Fort Collins, Colorado. Additional specimens are stored in the Department of Bioagricultural Sciences at Colorado State University in 95% ethanol at −20 °C, as they may be useful in future molecule-assisted species identifications.Males were cleared in a 5% KOH solution for 7–8 h , and theFor scanning electron microscopy, specimens were initially prepared by fixing in 2.5% glutaraldehyde in 0.15 M sodium phosphate buffer, pH 7.4, at 4 °C for 24–48 h. Post-fixation was carried out in 1% buffered osmium tetroxide overnight at 4 °C, then samples were dehydrated through a graded ethanol series, followed by critical point drying using a BioRad E3000 critical point dryer , or by dehydration with acetone and hexamethyldisilazane. All samples prepared for SEM were sputter coated with 10 nm gold using a Hummer VII . Micrographs were taken using a JEOL JSM-6500F Field Emission Scanning Electron Microscope at the Central Instrument Facility, Imaging Laboratory, located at Colorado State University. All images were captured digitally as tiff files, and graphically edited to input black image backgrounds . All measurements were taken at the widest or longest point of a given structure , and areIn life, adult males are orange to brown with clear to iridescent wings. Excluding the head, the body shape is robust, subtriangular with long, distinct legs, and an elongated genital segment . Many spThe head is relatively angular, and distinctly separate from the thorax. Dorsally, the head is approximately pentagonal with rounded edges, and is generally ovoid laterally . The heaAntennae: The filiform, has 10 segments, with distinct scape (scp) and pedicel (pdc); the total antennal length is 500–584 μm (mean 529 μm); the mean ratio of body length to antennal length is 1:1.94 μm. The antennal segments all bear numerous long setae. The scape is 32–55 μm (mean 41 μm) in length, widest at the base 38–44 μm (mean 41 μm), with few setae. The pedicel is 46–53 μm (mean 49 μm) in length, 32–32 μm (mean 32 μm) in width at the base, with numerous setae. Long, conspicuous setae are present on most of the head, body, and appendages. Much of the exoskeleton has a granular surface, including the simple eyes . PolygonThe thorax measures 357–424 μm (mean 395 μm) in length, and 378–433 μm (mean 416 μm) in width.Prothorax: Small lateral pronotal sclerite (prn) are well-defined, approximately triangular; the pronotal sclerite and pronotal ridge are situated posterior to the head. The ventral prosternum (stn1) is 172–202 μm (mean 183 μm) in length and 332–407 μm (mean 370 μm) in width, articulating anteriorly with the posterior edge of procoxa (cx1); the posterior edge of the prosternum is situated anterior to the marginal ridge (mr) of the basisternum.Mesothorax: Widest point of the body. The prescutal ridge (prscr) is 63–84 μm (mean 75 μm) in length and 126–139 μm (mean 132 μm) in width, laterally raised over the less-sclerotized prescutum, similar to an “awning” (2), situated posterior to the scutellum, is posteriorly rounded with a distinct anterio-distal curve. The scutellum and mesopostnotum are separated by the posterior notal wing process (pnwp); the metapleural ridge (plr3) runs along the posterior margin of the mesopostnotum. Mesopostphragma (phr2) are weakly sclerotized, situated posterior to the axillary cord and articulating with sublateral hamulohalteres on each side.“awning” . The dor“awning” . The scuThe dorsolateral portion of the mesothorax has a prealare ridge (prar). Tegula (teg) have 6–8 tegular setae (tegs). A small, rounded additional sclerite (asc) is present on the mesothorax and posterior to the hamulohaltera (h). Prealare and this additional sclerite articulate sublaterally with the costal complex of the wing vein (ccx).2) is proximal to the subepisternal ridge (ser). Postalare (pa) is situated dorsal and posterior to the mesepisternum. The basisternum (stn2) is a large, subrectangular, shield-like plate with margins strongly sclerotized, 105–143 μm (mean 128 μm) in length and 202–231 μm (mean 214 μm) in width at the widest point. The anterior edge of the basisternum is bordered by the marginal ridge; the posterior edge is bordered by the precoxal ridge (pcr2), and partially covers the furca (f) and furcal pit (fp).Laterally, the mesepisternum (epsSpiracles: The mesothoracic spiracle (sp2) and metathoracic spiracle (sp3) are situated sublaterally, with peritreme widths measuring 12–19 μm (mean 14 μm) and 12–14 μm (mean 13 μm), respectively, at the widest point. The peritreme is large and distinct  ventral setae. Dorsal setae are absent.Wings: Each wing is 820–943 μm (mean 868 μm) in length, extending past the apex of the abdomen and with a distinct alar lobe   A. Small,Legs: Pro- and mesothoracic legs are almost subequal in length, with the metathoracic legs being shortest. The mean ratio of prothoracic leg to total body length is 1:0.58 μm. The mean claw length is about 22 μm, similar to the width of the tarsal base. The tarsus has two tarsal digitules (tdgt), each 25–32 μm (mean 29 μm) in length, arising from the dorsal to the claw. The claw has two ungual digitules (ugdt), each approximately the same in length as the claw, arising ventrally at the point of attachment of the claw to the tarsus ; the width at the third abdominal segment is 202–256 μm (mean 231 μm). All abdominal segments have numerous long setae (aps). There are 9–18 (mean 13) abdominal ventral setae (avs) on each of segments 2–4; 5–15 (mean 10) on each of segments 5–7; 1–3 (mean 2) on abdominal sternite 8, and 6–15 (mean 11) on the genital segment. Dorsal setae are absent. Setae of the glandular pouch (glps) are present in two bundles; each seta is about 123 μm in length, arising from the glandular pouch on abdominal segment 8, often together with numerous wax excretions along the entire length .Genital segment: The style (st), is 101–122 μm (mean 113 μm) in length from the rounded apex to the posterior margin of abdominal segment 8, extending beyond the penial sheath (ps). The penial sheath, from the apex to the basal ridge, is 101–122 μm (mean 113 μm) in length and 23–25 μm (mean 25 μm) in width at the widest point. The aedeagus (aed), with distinctly sclerotized margins, lies within the penial sheath. In lateral view, the aedeagus curves slightly ventrally away from the style. Approximately six genital segment setae (gts) are present on each side of the ninth abdominal sternite. Excretions of wax are numerous on and around the style and genital segment.Allokermes available was that of A. kingii, collected at Blacksburg, (Montgomery County) Virginia [A. galliformis is now possible, and we found several diagnostic characteristics unique to A. galliformis as compared to A. kingii. In A. galliformis, the head is approximately subtriangular (it is rounded in A. kingii); the body is substantially more robust at the scutum and more tapered posteriorly in A. galliformis than in A. kingii; furthermore, the genital segment is more abruptly narrowed in A. galliformis than in A. kingii. Allokermes galliformis also lacks the dorsal abdominal setae that are present in A. kingii. Prior to this work, the only description of adult male Virginia . A compaKermes echinatus [K. nahalaii [A. galliformis has a substantially more robust prothorax with a broader connection to the head; the body also tapers more strongly posterior to the scutum, and the genital segment is narrower. Furthermore, the setae of the glandular pouch in A. galliformis are thicker and longer; only pleural and ventral setae on the abdominal segments are present as the dorsal abdominal setae are lacking, whereas they are not in Kermes species.When compared to males of species in a closely related genus, chinatus ,20 and Knahalaii ,21, A. gAllokermes species using routine molecular techniques such as the COI barcode [A. galliformis males is therefore a promising new tool for correctly identifying these scales at the species level, as other identification tools remain limited [Currently, it is not possible to distinguish between  barcode ,22, and  barcode  have not limited ,24. HoweAllokermes galliformis  (Hemiptera: Coccomorpha: Kermesidae) collected from drippy blight diseased trees in Colorado, United States of America. Morphological characteristics such as the subtriangular head, tapered body and genital segment, and the number and arrangement of setae can be used to separate A. galliformis from A. kingii, as well as relatives in the closely related genus Kermes. This paper describes and illustrates the morphological characteristics of the adult male of


P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis.To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group ( Stroke, which kills more than 2 million people every year in China, is the second leading cause of death . AccordiIn recent years, with the continuous improvement of research technology, there is a new understanding of the relationship between epigenetics and disease, and DNA methylation is a very important field in epigenetics research . DNA metAt present, some studies have confirmed that abnormal methylation of gene promoters is associated with IS . To clasP < 0.05), including 608 hypermethylated and 682 hypomethylated DMPs, were recognized. As per the annotation, 870 DMPs were actually found within 693 unique genes (DMGs). The heatmap and volcano plot of the DMPs are presented in First, we determined DNA methylation levels at 485578 methylation sites in carotid plaques in GSE66500. After quality control and screening, 20019 methylation positions were subjected to differential analysis. In total, 1290 DMPs (|Δβ| > 0.05 and detection P < 0.01–0.001)  that best discriminated between patients with and without symptoms . These f1–0.001) . The metThe chromosome distribution of differentially methylated intergenic CpGs is shown in P < 0.05. Approximately 18 pathways were enriched in the KEGG pathway analysis, and none of the DO items were analyzed for the screened DMGs with adjusted-P < 0.05. However, if the threshold value was set at P < 0.05, we could include 39 DO items for further analysis.As shown in Among these terms, GO:0035637 multicellular organismal signaling, GO:0007265 Ras protein signal transduction, hsa04659 Th17 cell differentiation, hsa05321 Inflammatory bowel disease (IBD), hsa04024 cAMP signaling cascade, hsa04151 PI3K-Akt signaling cascade and hsa05320 Autoimmune thyroid disease were confirmed in previous references to be associated with IS, and the genes associated with these terms were chosen for additional evaluation.Data analysis was done on the STRING database, which revealed 1463 protein pairs and 552 nodes with a combined score > 0.9. HLA-DRB1 and HLA-DQB1 was lesser in stroke patients than in normal controls (P < 0.05).First, we validated these two genes in different microarray datasets. As shown in Then, we implemented a correlation analysis to distinguish if DNA methylation caused IS through regulation of gene expression. Generally, the increase in DNA methylation affects the binding of transcription factors, leading to abnormal gene transcription, usually inhibiting transcription and resulting in the downregulation of gene expression. However, it was not absolute. In any case, changes in methylation can cause changes in gene expression.HLA-DRB1 and HLA-DQB1 gene methylation levels were negatively associated with their expression . The 322 validation samples were coordinated for age and sex. The weight, BMI, waist circumference, smoking status, serum TC and LDL-C levels were higher in IS patients compare to controls . Initialpression . This reIschemic stroke (IS) is a complicated disorder with great mortality as well as long-term disability outcomes. In spite of many concerns about stroke risk factors as well as prophylactic treatment, the number of stroke cases has been increasing recently, probably due to the increasing age of the population . The patMTRNR2L8 was a diagnostic biomarker for stroke and may also be a potential therapeutic target [ABCA1 gene and promote the reverse flow of cholesterol, weakening the trend of atherosclerosis. Interestingly, the study was validated only in women [Epigenetics is receiving increasing attention as it might contribute to the research of complex diseases and might also produce valuable biomarkers. Epigenetic mechanisms, for example DNA methylation, control higher-order DNA structure as well as gene expression. In recent years, with the continuous development of technology, the correlation between genome-wide methylation and IS has gradually been confirmed . Shen etc target . Fujii ein women .HLA-DRB1 and HLA-DQB1 genes have been proved to play an important role in the process of immune inflammation. Changed in their expression levels may eventually resulted in inflammation of intracranial arteries, leading to IS. Previous studies have confirmed that these two genes are clearly associated with IS [HLA, which is defined as the human major histocompatibility complex, functions as an essential element of the immune system. The major HLA antigens are HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DP, and HLA-DQ. HLA molecules have an imperative role in the transplantation reaction and immune response to various immunogens as well as infections . In addi with IS , 24.We used other datasets for verification and found that these two genes were significantly expressed at low levels in the IS population. Interestingly, we validated this conclusion in only one dataset, and there was no difference in the relative expression of these two genes within 24 hours and 24–48 hours after symptom onset. The reason for this was related to the small sample size of the dataset. Therefore, we found IS patients and healthy people in order to extract peripheral blood and at the same time, to verify the methylation and relative expression of the promoter regions of these two genes. We found that when the methylation of the promoter region increased, the gene expression decreased significantly, and methylation and expression were clearly correlated. The above conclusions are consistent with previous research results.vivo or in vitro.We have to admit the limitations of this study. First, the validation sample is small, and patients in this study are from two hospitals; hence, there may be differences with patients from diverse areas and of different races. Second, the precise mechanism of the (DNA methylation)–mediator (mRNA)–outcome (IS) network for controlling the pathological processes of IS has not been abundantly confirmed in In brief, we acquired the GSE66500 dataset from GEO and identified DMPs and genes. We chose 2 DMGs for validation in additional datasets and acquired 322 samples . HLA-DRB1 and HLA-DQB1 were found to exhibit hypermethylation and downregulated gene expression in IS patients. In addition, correlation analysis revealed that DNA methylation instigated IS through the regulation of gene expression.2 fold-change| (Δβ) > 0.05 and P < 0.05. GSE118481, GSE16561 [GSE66500  was retrGSE16561 , GSE2225GSE16561  and GSE3GSE16561  were alsGSE16561  to transGSE16561 . If a ge2 fold-change| ≥ 2 and P < 0.05. Then, we used GEO2R to identify the differentially methylated positions (DMPs) by comparing the normal and obese subjects. DMPs positioned in the gene region were allocated to the analogous genes that were defined as differentially methylated genes (DMGs). The threshold was set at |log2 fold-change| (Δβ) > 0.05 and P < 0.05. Subsequently, we matched DEGs to DMGs, and simply the matched genes (DEMGs) were chosen for additional examination.We compared obese subjects with controls to explore the differentially expressed genes (DEGs) with the limma package in R . The thrP < 0.05 along with false discovery rate (FDR) < 0.05. To further determine the location of hub sites in the dataset, shrunken centroid classifier analysis was performed with the “pamr” package in R [Analyses on large-scale transcription data or genomic data were generally done depending on functional enrichment analyses. These include disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway as well as gene ontology (GO) analyses. In the current study, we used clusterProfiler  along wiage in R .The protein prediction as well as experimental interactions was examined by the STRING database (version 11) . Gene fuFirst, we validated the hub genes in other expression datasets to explore the relationship between hub genes and IS in different dimensions. GSE118481 reflected the expression level of core genes in carotid plaques between cerebral ischemic symptoms and asymptomatic conditions. GSE16561 and GSE22255 indicated whether the comparative expression of hub genes was different among stroke patients and normal controls. GSE37587 further evaluated the relative expression level of hub genes in patients with cerebral infarction at different time points after symptom onset. Next, we sought out stroke and healthy control groups to extract peripheral blood for core gene validation.th Revision). Subjects with an embolic brain infarction, stroke triggered due to inflammatory disease, cardioembolic stroke, autoimmune disease, or serious chronic conditions were omitted from the current study [A total of 322 subjects with complaints related to the brain at the First People’s Hospital of Nanning City from Jan. 1, 2015, to Dec. 31, 2017, were recruited. The blood biochemistry levels were 3.10–5.17 (TC), 0.56–1.70 (TG), 0.91–1.81 (HDL-C), 2.70–3.20 (LDL-C) mmol/L, 1.00–1.78 (ApoA1), 0.63–1.14 g/L (ApoB), and 1.00–2.50 (ApoA1/B), which were stated as the standard values . All of nt study . The connt study .Genomic DNAs from the 322 peripheral blood samples were obtained with a TaKaRa MiniBEST Universal Genomic DNA Extraction Kit Ver.5.0. DNA concentrations were determined by means of a NanoDrop2000 spectrophotometer (USA). The methylation levels of CpG sites were assessed through pyrosequencing. PyroMark Assay Design software (Qiagen) was utilized to design precise sets of primers for CpG PCR amplification as well as sequencing. The primers can be found in st strand cDNA Synthesis Kit  as per the supplier’s instructions. Real-time polymerase chain reactions were carried out to evaluate the mRNA expression levels of hub genes using SYBR Premix Ex Taq II  by using a 7500 Real-Time PCR system . GAPDH served as an internal control. The primer sequences are mentioned in Total RNA from the 322 peripheral blood samples was extracted by means of an Axygen RNA Isolation Kit (USA) as per the supplier’s protocol. RNA concentrations were determined by means of a NanoDrop2000 spectrophotometer (USA). cDNA was synthesized from 1 μg of total RNA using a PrimeScript 1Data analyses were done using SPSS 22.0 (SPSS Inc. USA) and Prism 8.0 (GraphPad Software). Chi-square analysis was implemented to evaluate differences in ratios amongst groups. Continuous data are presented as the means ± SD for those that were normally distributed; the median and interquartile ranges of TG were not normally distributed. The Mann-Whitney nonparametric test and Kruskal-Wallis test were utilized to compare continuous data sets. R software (version 3.6.0) was utilized for further bioinformatics analysis. To define if the methylation level was related to gene expression, we conducted a correlation test between methylation and expression using the ggplot2 package in R.Supplementary Table 1Supplementary Table 2Supplementary Tables 3 and 4


Previous research has noted trends of increasing internalizing problems , particularly amongst adolescent girls. Cross-cohort comparisons using identical assessments of both anxiety and depression in youth are lacking, however.i) the relation between birth cohorts and internalizing symptoms using linear regressions, and (ii) whether percentages of participants exceeding scale cut-off scores changed over time, using Cochrane Armitage Trend Tests.In this large twin study, we examined trends in internalizing symptoms in samples of 9 year old children and 15 year old adolescents, gathered from successive birth cohorts from 1998 to 2008 (age 9) and 1994–2001 (age 15). Assessments at age 9 were parent-rated, and at age 15 self- and parent-rated. We examined  had scores above cut-off on anxiety symptoms, but not on depressive symptoms. At age 15, a significantly increasing percentage of participants (both boys and girls) had scores above cut-off particularly on self-reported internalizing symptoms. On parent-reported internalizing symptoms, only girls demonstrated a corresponding trend.In line with previous studies, we found small changes over sequential birth cohorts in frequencies of depression and anxiety symptoms in children. Further, these changes were not exclusive to girls. N = 21 709) from 166 studies in total, demonstrated that girls show more internalizing symptoms than boys overall, even though the differences were small [Epidemiological studies have indicated that mental health problems in youth are common and tend to persist into adulthood . An estire small . The terN = 15,000; 15–16 years old) used repeated cross-sectional assessments of psychosomatic health problems during 1988–2005. The results demonstrated successive increases in psychosomatic health problems specifically in girls across the study period [Understanding time trends in mental health symptoms is one important aspect in the prevention of youth mental illness . During y period . In paray period . It is uy period .i) the relation between birth cohorts and internalizing symptoms, and (ii) whether the percentage of participants exceeding cut-off scores of the scales changed over time. Investigating temporal trends of internalizing symptoms is an important research endeavor to explore whether the increase in clinical parameters  of anxiety and depression during the past decades corresponds to actual increasing levels of internalizing symptoms.The rationale for this large population-based study was to examine trends in internalizing symptoms, both anxiety and depression, in consecutive birth cohorts at age 9 (parent-rated) and age 15 (self- and parent-rated). We investigated (Participants were recruited from the Child and Adolescent Twin Study in Sweden (CATSS), which emanates from the Swedish Twin Registry (STR). The CATSS is an ongoing and nation-wide longitudinal study that aims to investigate mental and somatic health in childhood and adolescence, including all twins born in Sweden since July 1992 . When thThe current study involved samples of children and adolescents 9 and 15 years old, gathered from successive birth cohorts from 1998 to 2008 (age 9) and 1994–2001 (age 15).The response rate in the total sample at age 9 was 63.5%. The response rates for each birth cohort 1998–2008 respectively were: 69.9, 73.2, 71.4, 69.6, 73.0, 68.1, 60.3, 63.8, 69.2, 59.7, and 44.2%. Furthermore, the response rate in the total sample at age 15 was 60.1%. The response rates for each birth cohort 1994–2001 respectively was: 60.0, 57.4, 72.4, 61.2, 63.1, 54.7, 57.5, and 55.2%. The data collection took place between 2007 and 2017 for children age 9, and between 2009 and 2016 for adolescents age 15.The telephone-interview at age 9 included the following parent-rated scales:Screen for Child Anxiety Related Emotional Disorders (SCARED) is a 41-item screening instrument for anxiety symptoms, based on criteria in the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV), in children and adolescents aged 9–18 [not true), to 2 (= true), with a maximum score of 82. SCARED is one of the most commonly used scales to assess anxiety symptoms in children [H = .90 for all participants, .89 for boys and .89 for girls [The ged 9–18 , 15. Eacchildren . It is cchildren , across children , 20, andchildren . Cut-offor girls .Short Mood and Feelings Questionnaire (sMFQ) [Mood and Feelings Questionnaire (MFQ) [no), to 2 (= yes). Psychometric properties for sMFQ are satisfactory, with adequate internal consistency [H = .84 for all participants as well as for boys and for girls [The e (sMFQ)  is a 13-re (MFQ) , developsistency , 24–26, sistency , 28, andsistency , 26. Bassistency . The sMFor girls .Strength and Difficulties Questionnaire (SDQ), a 25-item screening measure developed to assess externalizing and internalizing symptoms in children and adolescents 4–16 years old [not true), to 2 (= certainly true). SDQ is extensively used in different settings  to screen for internalizing symptoms [The assessment at age 15 encompassed self-and parent-rated versions of the ears old . SDQ consymptoms , and it symptoms . We chossymptoms .H = .81 for all participants, .80 for boys and .82 for girls) [H values for the SDQ-Emotional self-report version were .73 for all participants, .66 for boys and .71 for girls. There was a moderate correlation between the SDQ-Emotional parent version and the SDQ-Emotional self-report version (Pearson’s r = .41).The SDQ-Emotional parent version revealed satisfactory scale reliability for all participants Coefficient r girls) . Coeffict-test for independent samples. Additionally, Cohen’s d was calculated (by dividing the mean difference by the pooled standard deviation) as a measure of effect size. To explore the relation between birth cohorts and internalizing symptoms, linear regressions were calculated. In these analyses, birth cohort served as the independent variable and individual total scale scores  served as dependent variables. Prior to the calculations, we checked the distributions of the scores, and considered them approximately normally distributed.Internalizing symptoms were investigated using descriptive statistics . Sex differences between completers and non-completers of the scales were investigated through chi-square tests whereas sex differences in scale scores were computed using To explore whether the percentage of participants exceeding cut-off scores of the scales changed over time, Cochrane Armitage Trend Tests (two-sided) were computed. Both sets of twins were used in all analyses. A cluster robust sandwich estimator was applied to adjust the standard errors for the nested twin data when computing the regression models. Analyses were computed in the total sample, and with boys and girls separately.χ2  = 3.06, p = .080, χ2  = 2.01, p = .156). However, a larger proportion of boys were found among the completers (48.2%) than among the non-completers (43.2%) of the SDQ-Emotional parent report  = 20.94, p < .001). In contrast, a larger proportion of girls were found among the completers (54.7%) of the SDQ-Emotional self-report than among the non-completers of this scale (39.4%)  = 131.83, p < .001). Moreover, among the completers, girls had significantly higher mean scores than boys on all scales except for the sMFQ where boys had slightly higher mean scores than girls. Effect sizes for the sex differences were negligible for the SCARED and sMFQ (Cohen’s d = .09 and .04 respectively), small for the SDQ Emotional parent-report (Cohen’s d = .38) and large for the SDQ Emotional self-report (Cohen’s d = .81).The number of participants completing each scale ranged between 9821 and 17562, with an approximately equal distribution of boys and girls (see Table p < .001). Additionally, the regression analyses with the sMFQ as the dependent variable were statistically significant for the total sample (p = .024) but not for boys and girls separately. The positive beta-coefficients in the regressions reaching significance suggested positive relations between birth cohorts and the SCARED and sMFQ respectively , and for both boys (p < 0.001), and girls (p = 0.003) when their results were analyzed separately. There were no such trends for the sMFQ  and for girls (p = .001) but not for boys. The analyses with the SDQ-Emotional self-report version 1as dependent variable yielded significant models for the total sample and for both boys and girls (p < .001). The positive beta-coefficients in the regressions that reached statistical significance suggested positive relations between birth cohorts and outcomes , boys (p = .008) and girls (p < .001) respectively. For girls, there was a corresponding trend of scores above cut-off on the SDQ-Emotional parent version (p = .003). There were however, no such trends for the total sample, or for boys , there were no significant changes in mean scores on depression and anxiety across time for children 10–11 years old and 12–13 years old, but a significant and small increase across time for youth 14–15 years old [In contrast to our findings, a meta-analysis of 26 epidemiological studies based on clinical interviews, did not find evidence of increasing rates of child and adolescent depression during a 30-year observation period beginning in the mid 60’s . Also, iThere are several unique aspects of the current study. To our knowledge, this is the first population-based study with cross-cohort comparisons, using well-validated scales to assess symptoms of anxiety and depression separately. The CATSS-study is one of the most comprehensive twin studies of childhood mental and somatic health problems ever performed. Given the relatively high response rate  and the large study cohorts, the sample can be considered representative of the Swedish population. Additionally, this study adds to previous literature by assessing large cohorts and investigating boys and girls separately. Moreover, it includes later cohorts than previously reported in research , 11.The study also had several limitations. Firstly, we did not have separate measures for anxiety and depression at age 15. This is due to sacrifices in terms of extent to prioritize response rate at the follow-ups of the CATSS study . SecondlFinally, it is not possible to delineate whether the augmented levels of internalizing symptoms in the current study reflect a real increase in symptoms, an increased tendency to recognize or report these symptoms, or a combination of both. Future longitudinal studies utilizing register-based data linked with self-report should explore whether augmented levels of internalizing symptoms correspond with increasing levels of health care consumption.To our knowledge, this is the first study using well-validated measures to assess internalizing symptoms, i.e. both anxiety and depressive symptoms, across consecutive birth cohorts of youth. The results demonstrated some trends in internalizing symptoms across birth cohorts, for both boys and girls.In the current study including a large Swedish twin sample, slight increases in parent-reported internalizing symptoms at age 9 were observed across the years 2007–2017 for both boys and girls. At age 15, there was an increase in self-reported internalizing symptoms, during the years 2009–2016 for both boys and girls. This study contributes to the field through its methodological strengths; separate assessments of symptoms of depression and anxiety in representative community samples using repeated cross-sectional assessments.


Context: As an alternative approach, administration of phytotherapeutic agents in management of benign prostate hyperplasia (BPH), is rapidly growing each day. Different authors have indicated effectiveness of Viola odorata L. (Violaceae), Echium amoenum Fisch. & C.A.Mey. (Boraginaceae) and Physalis alkekengi L. (Solanaceae) in treatment of BPH. However, none have reported the beneficial outcomes of the mixture yet.Objective: This study evaluates the therapeutical effects of V. odorata, E. amoenum and P. alkekengi mixture on symptomatic BPH patients.Materials and methods: Eighty six symptomatic BPH patients with International Prostate Symptom Score (IPSS) of more than 13 and prostate volume of more than 30 cm3 were randomly allocated to receive a two-week course of placebo (control group) or 1 mL of mixed hydro-alcoholic solution of P. alkekengi, E. amoenum and V. odorata extracts  (treatment group).Results: IPSS score of incomplete urination (42.3 ± 2.04%), frequency of urination (20.08 ± 1.02%), intermittency (40.78 ± 2.16%), urgency (60.91 ± 3.14%), weak stream (50.58 ± 2.14%), straining (55.67 ± 2.53%) and nocturia (40.14 ± 1.89%) in treatment group were significantly decreased after treatment compare to placebo receiving group. Furthermore, the prostate volume (16.92 ± 0.89%) and extant urine volume (28.12 ± 1.36%) also significantly decreased in treatment group compared to control group. No significant side effects or abnormalities in biochemical tests and urinalysis were observed throughout the study.Discussion and conclusions: Based on results, mentioned mixture is safe and effective in improving life quality of patients suffering from BPH. Benign prostatic hyperplasia (BPH) is considered as the most prevalent urologic disorder in elderly men with prevalence rate of more than 70% at 60 years old age and 90% older than 70 years. It is mostly diagnosed by stromal and glandular cells hyperproliferation around periurethral areas and transition zones of the prostate gland , Echium amoenum Fisch. & C.A.Mey. (Boraginaceae) and Physalis alkekengi L. (Solanaceae) are three of these agents applied in current study.As an alternative therapy in BPH, phytotherapy or administering plant extracts with therapeutic purposes to manage BPH, is rapidly growing each day  and case group (n = 57). Demographic data of studied groups are presented in Current randomized, double blind, 2-week placebo-controlled single centre trial was performed to evaluate the efficacy of Male patients with confirmed BPH diagnosis through medical history physical examination including a digital rectal examination (DRE);Aged between 40 and 75 years old;3 diagnosed by transrectal ultrasonography (TRUS);Prostate volume of more than 30 cmInternational Prostate Symptom Score (IPSS) of more than 13 at the screening time;Patients which were able and willing to give their written informed consent.The trial was conducted in accordance to the ethical considerations of the ‘Declaration of Helsinki’ and subsequent amendments thereof (Nuremburg protocol). The committee of ethics at the Baghiatallah University of Medical Sciences  approved the protocol of the study (Reference number: IR.BMSU.REC.1394.246) and written informed consents were collected from subjects before inclusion in the study. Subjects were considered eligible for inclusion in this trial only if all of the following criteria were applicable:Patients with diabetes, hypertension, cardiovascular disorders, hyperlipidaemia, history of cardiac apoplexy, cerebral apoplexy, ischemic attack, urinary infectious vessels or prostate and also the ones treated with anti-BPH drugs within a month before the beginning of study or sensitive to applied medicinal plants in the study were excluded from participation.P. alkekengi fruits (voucher 975) were collected from Guilan province in September 2014, E. amoenum flowers (voucher 976) were collected from a farm at 80 km north of Ghazvin province in March 2014 and V. odorata flowers (voucher 977) were collected from Mazandaran forest, Mazandaran, Iran in April 2014. A voucher specimen of each plant was identified by Dr. Abbas Hadjiakhoondi and deposited in Herbarium of Pharmacy School, Tehran University of Medical Sciences Tehran, Iran.Plant materials were collected throughout the year 2014 from different zones of Iran. P. alkekengi, E. amoenum and V. odorata extracts with final concentration of 1.5, 1 and 1.5%, respectively.All plant materials were air-dried at room temperature in the shade before extraction. After grinding, 50 g of each dried plant material was mixed and extracted with 80% ethanol by repeated maceration (2 × 48 h). The solvent was completely removed under reduced pressure using a rotary evaporator apparatus. Dried extracts were kept at 4 °C until usage. Final applied formulation in the study was a mixed hydro-alcoholic solution of Patients received 1 mL of assigned extract twice daily  for 2 weeks. Assigning the baseline visit (week 0), patients returned 2 weeks later to urology department for assessing the safety and efficacy of treatment. The value of haemoglobin (Hb), haematocrit (HTC), platelets (PLT), neutrophils, lymphocytes, and basophiles in blood were checked during the trial. Also serum electrolytes, fasting blood sugar (FBS), creatinine, BUN, elements (K) and enzyme activities  were measured during the study. Serum examination for measuring prostate specific antigen (PSA) was also performed. IPSS was utilized for evaluating the validity of patient’s symptoms and responses to therapeutic protocol and further comparing the results among control and case groups. Finally, the rate of urinary excretion abnormalities such as nocturia, incomplete urination, frequency, intermittency, urgency and strength of urine flow were also evaluated before and after the therapy. All episodes of adverse effects such as hypertension, nausea, vomiting, dyspepsia, diarrhoea, constipation and rash were also recorded throughout the study.t-test or ANOVA with Bonferroni’s adjustment for multiple comparisons. A probability of less than 0.05 was considered as significant. Data were analysed using SPSS, version 16.5 .All data were analysed using Student’s Assortment of eligible subjects, meeting all inclusion criteria was begun in February 2015 and ended in April 2015. As depicted in Several studies have depicted different restrictions in association with BPH therapy by different classes of chemical drugs and invasive procedures including surgery. For instance, administration of Finasteride results in significant decrease in libido and requires a long period of time before it begins its beneficial effects, or α blockers can result chest pain, irregular heartbeats and impotence (Gormley et al. P. alkekengi extract significantly reduced testosterone level which may contribute to the decrease in the size of prostate (Naser et al. P. alkekengi fruit extract induces a significant antispasmodic effect on uterus of rats mainly through blocking Ca2+ and partially via inhibiting NO synthesis and antagonizing β-adrenoceptors (Gharib Naseri et al. In a recently performed study, it was clearly demonstrated that administration of V. odorata (Dweck Several studies have identified the presence of β-sitosterol as an effective component in ta Dweck . β-Sitosta Dweck . Based oE. amoenum extract demonstrates several anxiolytic, antidepressant, anti-obsessive compulsive and sedative effects, all of which can significantly improve the quality of life, self-esteem and prolong life expectancy (Sayyah et al. Notably, however, a significant relationship has been reported between depression and anxiety and LUTS in several studies over last few decades Engel . This asAs mentioned previously, inflammation is another factor mostly involved in BPH etiology and as the extracts of these three plants are all effective anti-inflammatory agents, the other results of this effectiveness is attributed to this point. At the end the diuretic effects of the administered mixture can further improve the urinary flow rate. The other important result obtained in this study was that the urgency was not affected by this mixture which may be related to the diuretic effects of these plants.Adverse effects, such as nausea, vomiting, dyspepsia, diarrhoea, constipation, rash and hypersensitivity did not differ significantly between groups before and after the trial. Furthermore, the quality of life was improved in treatment group according to patient’s answers.Viola odorata, Echium amoenum and Physalis alkekengi extracts, as naturally occurring compounds, can safely and effectively improve LUTS in symptomatic BPH patients and be considered as a convenient treatment choice for BPH treatment. However, it is difficult to state with certainty whether the same results could be observed through applying merely one or two of the plant extracts presented in the mixture. P. alkekengi, V. odorata and E. amoenum have shown to be successful at least partly, when administered individually. Since each plant possess slightly different mechanisms and time frame of action, it appeared more logical to evaluate the combination of extracts to identify clinical utility first. At the end, further studies for comparing the therapeutic outcomes of each component individually with mixture and investigating whether extending duration of therapy could further affect the final outcomes seems to be essential.Based on results obtained in current study, it can be concluded that administration of mixture of


Respiratory infections are the main indication for antimicrobial use in calves. As in humans and horses, studying inflammation of the deep airways by lung cytology raises the possibility of preventing respiratory disease and targeting its treatment in the future. Whether lung cytology findings coincide with clinical signs and lung ultrasonographic findings is currently unknown. Therefore, the objective of the present study was to determine the association of lung cytology with clinical signs, lung consolidation and broncho-alveolar lavage fluid (BALf) characteristics (including bacteriology).A total of 352 indoor group-housed calves aged between 1 and 6 months from 62 conveniently selected commercial herds were included in this cross-sectional study. Clinical examination, thoracic ultrasound and bacteriology and cytology on non-endoscopic broncho-alveolar lavage (nBAL) samples were performed.P = 0.04), standing posture (P = 0.03) increased breathing rate (P = 0.02) and isolation of Pasteurella multocida (P = 0.005), were associated with increased neutrophil percentage. No significant associations between lung ultrasonographic findings and cytology results were present, except for presence of basophils in BALf and consolidation of > 3 cm in depth . Abnormal lung sounds were associated with detection of eosinophils in BALf . Total nucleated cell count (TNCC) (P <  0.001) was positively and macrophage percentage (P = 0.02) negatively associated with volume of lavage fluid recovered. Macroscopic blood staining of BALf increased TNCC (P = 0.002) and lymphocyte percentage (P = 0.001).Pneumonia, defined as presence of ultrasonographic lung consolidations ≥1 cm in depth, affected 42.4% of the calves. Mean BALf neutrophil percentage was 36.6%  and only a positive induced tracheal cough reflex  contains supplementary material, which is available to authorized users. Respiratory tract infections have severe economic consequences for the cattle industry worldwide –3. In reThe objective of the present study was to determine whether clinical signs, lung ultrasound, and broncho-alveolar lavage fluid (BALf) characteristics (including bacteriology) are associated with lung cytology of nBAL samples in a population of indoor group-housed calves.The sample size required to detect a 10% difference in neutrophil percentage between calves with and without a given risk factor, using 5% as a reference as seen in healthy horses , was 139For each calf data on the following clinical signs was collected: mentation , posture , head tilt , position of the ears , nasal discharge , ocular discharge , type of ocular or nasal discharge , spontaneous cough , breathing frequency (in breaths per minute), heart rate (in beats per minute), rectal temperature (°C), induced laryngeal cough reflex , induced tracheal cough reflex , faecal consistency  and lung auscultation . A positive induced laryngeal or tracheal cough reflex was defined as a single induced cough following manual compression of the larynx or trachea, respectively.Thoracic ultrasound was performed with a linear probe with a frequency of 7.5-MHz , set at 8 cm of depth, using isopropyl alcohol (70%) as a transducing agent as previously described . PresencBALf was collected by a non-endoscopic technique using a reusable custom made polytetrafluorethylene catheter of 1.5 m length with a 12G- catheter stylet and an inner and outer diameter of 2 mm and 4 mm, respectively . The procedure was performed in standing, unsedated animals by the same veterinarian, using a new sterilized catheter for each calf as described previously . BrieflyTotal nucleated cell count (TNCC) of the recovered lavage fluid was determined manually using a haemocytometer. The sample was vortexed and 1 μL of BALf was diluted with 10 μL Türk’s solution  and counted manually using a Bürker counting chamber . Diff-Quick  stained cytocentrifuge  preparations of BALf (1200 rpm for 10 min) were made and a total of 400 nucleated cells was counted at × 100 magnification to calculate the differential cell count . All spePasteurellaceae and pleuropneumonia-like organism agar (PPLO) , for isolation of Mycoplasmataceae. Incubation was done at 35 °C and 5% CO2, overnight and for 5 days, for Pasteurellaceae and Mycoplasmataceae, respectively. Mycoplasma bovis was identified by inoculating colonies on a PPLO agar enriched with polysorbate 80 , followed by microscopic identification of growing colonies by their typical morphology ), P. multocida and M. haemolytica (1.4% [5/352]), M. bovis and M. haemolytica (1.1% [4/352]), M. haemolytica and H. somni (0.6% [2/352]) and P. multocida and H. somni (0.6% [2/352]) combinations. Pathogen isolation rates were not linked with clinical signs or ultrasonographic findings.A pure or a dominant culture for Log transformation was needed for TNCC, neutrophil percentage, lymphocyte percentage and epithelial cell percentage. Macrophage percentage was normally distributed. For eosinophil and basophil percentage no transformation to a normal distribution was possible, hence it was opted to analyse them as binary outcomes. When performing the final mixed model analysis 17 calves were excluded for the analysis of BALf neutrophils, lymphocytes and epithelial cells and 20 calves were excluded for the analysis of BALf TNCC and macrophages, due to incomplete information on some of the predictors studied, resulting in 335 and 332 calves for final analyses, respectively.The final multivariable models for TNCC Table , neutropP. multocida culture was associated with increased BALf neutrophil percentage and a reduction in macrophage percentage (Tables H. somni isolation was associated with detection of basophils (Table P = 0.04) with an increased BALf neutrophil percentage. Only for the presence of basophils a significant association with lung consolidation > 3 cm (P = 0.001) remained in the multivariable model  were present, despite that half of the calves studied did not show any abnormal clinical signs, was unexpected. This prevalence is higher than previously reported for 60-day-old Holstein heifers (20.2% (any consolidation)  and threThis study showed that in this population of animals, housed in herds with only endemic respiratory problems, no association of lung ultrasonographic findings and lung cytology was found. This is in contrast to previous work on experimental animals using an endoscopic BAL technique . Most liThe absence of a reference framework for nBAL cytology was a serious limitation for our study. Given the absence of good criteria defining a calf with healthy airways, this issue applies to all sampling techniques and the cross-sectional design of this study appeared the best option to gain first insights. A clear finding was that BALf neutrophil levels exceeded values previously reported in calves , 36, 37.P. multocida and an increased neutrophil and decreased macrophage percentage was demonstrated, as seen in another study [P. multocida could be a more virulent pathogen or a better secondary invader of airways that are already inflamed due to air pollution or viral infections, under the conditions of our study. In contrast to previous experimental studies, isolation of M. haemolytica was not linked to BALf neutrophil percentage, potentially due to differences in virulence between strains [H. somni isolation was not associated with neutrophilia, but increased both lymphocyte and basophil percentage. This might point towards a different type of immune response against H. somni. Given the low number of H. somni and M. bovis positive cases, the absence of an association between isolation of H. somni and M. bovis and an increasing neutrophil percentage should be interpreted with care.In addition to the aforementioned factors, bacterial infection would be a logical trigger of neutrophil influx, resulting in a very high neutrophil percentage –9. The uer study . Taking  strains , 44. H. Similar to BALf neutrophil percentage, TNCC counts exceeded values reported in previous work with the endoscopic technique . Cut-offH. somni isolation and presence of basophils in BALf points towards a similar mechanism in calves.Eosinophil and basophil percentages in BALf from young calves were studied for the first time in this paper. Abnormal lung auscultation was associated with a BALf eosinophil percentage > 1%. Wheezes, as induced by bronchoconstriction, were heard in 25% (6/24) of these calves. Next to parasitic infections, these findings could point towards the existence of asthmatic syndromes in calves, as well-known in humans and horses , 46, 47.Finally, an age effect for BALf cytological composition has been observed, characterized by higher lymphocyte and lower macrophage levels in BALf of older calves. The same age effects were demonstrated in peripheral blood . The posCytology findings as determined by an nBAL method, were only associated to a limited extent with ultrasonographic findings and selected clinical signs . BALf cytology offers additional information to the analysis of respiratory problems in calves, potentially aiding in better prevention and targeted treatment in the future. In this population, selected from herds not reporting any recent respiratory diseases, a high prevalence of lung consolidation and animals with neutrophilia was detected, pointing towards issues with possible unawareness of the problem or subclinical disease presentations.Additional file 1:Table S1. Broncho-alveolar lavage fluid total nucleated cell count and differential cell counts according to ultrasonographic lesion score (ULS) based on 352 group-housed calves. (DOCX 26 kb)Additional file 2:Table S2. Descriptives of broncho-alveolar fluid cellular characteristics from 352 group-housed calves. (DOCX 37 kb)


Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection.We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another.We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups.There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and mitochondrial trifunctional protein deficiency (MTPD) are rare autosomal recessive fatty acid β-oxidation disorders. Combined, they have an estimated prevalence of 1.02 per 100,000 live births worldwide .Neurological problems were reported in 4 studies , 24, 26.Muscular and motor problems were reported in six studies , 25, 26.The following three follow up analyses considered different subsets of the available individual patient data. Results of the follow up analyses are presented in Figs. n = 7) [Individual patient data reported in eight papers were used for the follow up comparisons of outcomes in asymptomatically vs symptomatically detected patients , 27–29. liver, visual, neurological, motor or muscular problemss between pre-symptomatically and symptomatically detected patients in the studies reporting data for these outcomes [There were no significant differences in the incidence of outcomes , 21–26.mortality rates in 5/6 analysed patient groups reporting on asymptomatic versus symptomatically detected patients [p = 0.01, age at death 7 days) [There was no significant difference in patients , 24, 28  7 days) .p < 0.05, median age at study end 17 years) [There was no statistically significant difference in the frequency of heart problems in 5/6 analysed patient groups , 24, 26.7 years) .Follow up analyses were undertaken to see how grouping people by whether they were detected through screening (including cascade testing) or outside of screening affected outcomes. Details are provided in Fig. p < 0.05) [Among the five studies that reported on mortality , 28, 29,p = 0.02) [Among the six studies reporting on heart problems , 26, 27, = 0.02) . The secp = 0.02) [Three studies reported on the incidence of liver problems , 13, 15.p = 0.03 [Six studies (from five cohorts) reported on eye problems , 24–26. p = 0.03 .p = 0.03) [Four studies reported on motor and muscular problems , 25, 26.p = 0.02) [Two studies explored hypoglycaemia (not as a presenting symptom), and are presented in , 22. One = 0.02) . They foFour studies were included in this follow up analysis , 25, 26 No statistically significant differences between groups were found for mortality (1 study ),  liverp < 0.05) [p = 1) [Differences in the incidence of heart problems were reported in two studies , 26. The < 0.05) . This wap = 0.05 [Three studies reported visual problems across the 3 separate groups , 25, 26.p = 0.05 . No statWe conducted a systematic review to examine the clinical outcomes of people with LCHADD/MTPD who received early dietary management following screening  versus later dietary management following the presentation of symptoms (either before or after the screening period). We included 13 articles, reporting on 11 patient groups. The methodological quality of all of the included studies was weak or moderate.From our narrative synthesis there appear to be fewer instances of heart and liver related problems in people with LCHADD or MTPD who are diagnosed earlier  than those diagnosed at a later age (following symptomatic presentation). However, it is not clear whether these differences are due to a beneficial effect of screening or biases in study design, and it is less clear whether there is any reduction in mortality following screen-detection. Mortality may occur earlier in those the early screen detected group. This may be due to these newborns being symptomatic at diagnosis and having a more severe form of the disease. 6/13 studies , 28, 29 A related review we undertook highlighted an issue in the indexing of some search terms in MEDLINE. The phrase “inborn errors of metabolism” had not been indexed as a MeSH heading, so further searches were done using this phrase as a key word search. Only one additional paper was identified that was relevant for this review.Our systematic review has a number of strengths. To our knowledge, this is the first systematic review comparing the outcomes of LCHADD and MTPD patients following pre-symptomatic detection or clinical detection after presenting with symptoms. We conducted a wide-ranging exhaustive search with no limits on date or language, independent literature screening and quality appraisal were undertaken by two reviewers, and all data extraction forms were checked by a second reviewer. However, there are also some limitations. Although we did not exclude studies on the basis of language, the search terms were in English so may have missed papers in other languages.statistical significance in the observed comparisons, but given the very few number of patients who have these disorders, it is important to also consider the clinical significance. Avoiding cardiomyopathy and hepatomegaly is of serious clinical importance to patients. On the other hand, enforcing a restricted diet on patients who have screened positive but who remain asymptomatic and may have never gone on to become symptomatic, may seriously affect their quality of life.Drawing conclusions from the follow up analyses should be interpreted with caution due to the small sample sizes. This review considers the Evidence is still very limited and at risk of bias. Further investigation is needed regarding whether the cases of LCHADD and MTPD detected by screening represent the same spectrum of disease as those detected clinically, and whether all screen-detected babies would go on to become symptomatic. Confounding factors such as age at time of study, follow-up time, possible repetition of patients across cohorts, genotype and severity of disease must all be considered. Analyses of genotype phenotype correlations might be of assistance in the future. Likewise, large international collaborations may help provide a clearer picture on whether pre-symptomatic treatment results in better outcomes.There is some evidence to suggest that pre-symptomatic dietary management may help delay or prevent the onset of some LCHADD and MTPD related long-term complications. However, studies have not been large enough to show any consistent significant benefits, and many confounding factors such as genotype, disease severity, age at diagnosis, and follow-up time between ‘early’ and ‘late’ treated groups have not been accounted for. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention being paid to disease severity and treatment group.Additional file 1. Search strategies.Additional file 2. Data extraction form for primary studies.Additional file 3. List of excluded studies and reasons.Additional file 4. Methodological quality of included studies.Additional file 5. Follow up analyses.