However, data failed to reach a significant difference after excluding the child with blood mercury exceeding the toxic value. The findings indicate that KD patients with lower sodium concentrations had a remarkably higher proportion of intravenous immunoglobulin (IVIG) resistance (p = 0.022). Our patients who had lower mercury levels (<0.5 μg/L) had more changes in bacille Calmette-Guerin. Mercury levels in 14/14 patients with coronary artery lesions and 4/4 patients with IVIG resistance were all measured to have values greater than 1 μg/L . Mercury levels had no correlations with IVIG resistance or coronary artery lesion (CAL) formation (p > 0.05). CAL development was more common in the incomplete group than in the complete KD group (p = 0.019). In this first report about mercury levels in KD patients, we observed that the juvenile Taiwanese had higher mercury concentration in blood compared to other populations.The risk of ethnic Kawasaki disease (KD) has been proposed to be associated with blood mercury levels in American children. We investigated the blood levels of mercury in children with KD and their association with disease outcome. The mercury levels demonstrated a significantly negative correlation with sodium levels ( Kawasaki disease (KD) has become more prevalent in recent years and is the most common cause of pediatric acquired heart diseases . A globaOxidative stress can be stimulated via contacting mercury in the form of methylmercury crossing the blood–brain and placental barriers, which may occur through fish consumption, vaccination, or environmental contamination by disposed personal computers or local industrial emissions in Taiwan . MethylmIn 2015, Sharma et al. summarized that mercury concentration in the peripheral blood was highest in Africa, followed by South America or Asia and lowest in Europe and North America . In our This study was developed in the Kaohsiung Chang Gung Memorial Hospital and carried out between 2016 and 2020. We enrolled a total of 85 KD patients. Subjects consisted of 48 boys (56.47%) and 37 girls, aged 0 months to 6 years. Ethical approval for the study was obtained from the Chang Gung Medical Foundation Institutional Review Board (IRB 201601736A3). KD was diagnosed in line with the American Heart Association diagnostic guidelines for KD [Total blood routine lab data were determined prior to intravenous immunoglobulin (IVIG) infusion. Echocardiography was performed in the acute stage of KD as previously described in our report . PatientWe collected 3 mL whole blood samples in K2EDTA tubes . The tubes were placed at 4 °C for the evaluation of total Hg later. Clotted whole blood was disallowed and rejected. The detection limit of the assay was 0.2 μg/L. To analyze mercury levels in the whole blood, the Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) technique on PerkinElmer NexIon 300  equipment was used and reported as micrograms per liter (μg/L). The laboratory conducted blanks for quality control daily.U test for continuous values to calculate the numeric values, the chi-square test was for comparing categorical values, and Pearson’s correlation to estimate the relationships between blood biochemistry and mercury levels. All p-values were 2-sided with alpha values less than 0.05 considered statistically significant.Statistical tests using the Statistical Package for Social Sciences (SPSS)  were analyzed. We carried out non-parametric tests for the statistical analyses according to variable distributions as follows: the Mann–Whitney We identified a comparable concentration of total mercury in the whole blood of populations susceptible to KD in the literature published in English. An extensive search of children and adolescents under the age of 18 years old as target groups was carried out on PubMed and included hand-searched references and screened citation lists. The keywords were “mercury AND blood AND child”. We identified relevant articles using the mercury measurement unit, μg/L. We excluded those reports without juvenile blood mercury data. This search turned out 840 peer-reviewed articles reported before 20 February 2020. We ultimately chose a total of six peer-reviewed studies including relevant age and our current reports for data extraction ,25,26,27From each eligible study, we found the central value  of mercury data. In surveys that only recorded the arithmetic means of blood mercury, we assumed that the data were normally distributed and took the arithmetic mean to be as a representative of central value as median. In the further steps of data treatment and analysis, the (Maximum—Minimum)/4 formula was used to estimate the standard deviation . We subsn = 85) was 1.90 ± 0.14 years, and the male-to-female ratio was 1.30 (48:37). Among the total patients, 68 presented with complete KD and 17 with incomplete KD. The prevalence rates of the clinical symptoms of the eyes, oral changes, polymorphous rashes, extremity edema, palpable cervical lymphadenitis, and BCG scar reactivation were 94.1%, 90.6%, 87.1%, 87.1%, 38.8%, and 63.6%, respectively. Fourteen children (16.5%) demonstrated echocardiographic abnormalities in the acute stage. CAL development was more common in the incomplete group than in the complete KD group . Four children did not respond to initial IVIG treatment. All four IVIG-resistant patients had BCG scar activation, polymorphous rash, swelling of extremities, conjunctival congestion, and changes in oral mucosa and belonged to the complete KD group, but this finding did not reach statistical significance.The mean age of KD patients (n = 79) but included undetected data in the analysis for categorical mercury variable (n = 85). No statistically significant difference was found in mercury levels (p = 0.448) between male and female KD patients prior to IVIG treatment. Furthermore, no correlation was observed in age or pre-IVIG mercury levels . Pre-treatment mercury levels > 1 μg/L were detected in all of the KD patients with CAL or IVIG resistance without a significant difference. For patients with mercury > 1 μg/L, we observed a borderline significant difference between CAL and non-CAL groups (p = 0.058). No significant difference was found in mercury levels between IVIG-responsive and IVIG-resistant groups (median: 3 (interquartile range 1.80–5.70) μg/L vs. 5.4 (1.65–8.93) μg/L, p = 0.553), nor in patients with complete and incomplete KD (2.9 (1.80–5.68) μg/L vs. 3.5 (1.5–6.40) μg/L, p = 0.900). No significant association was observed between mercury levels and BCG site reaction or clinical features of KD presented (p = 0.045). Age at onset was significantly lower in the BCG change group . The blood mercury concentration in the five age and gender matched non-KD control group (4.42 ± 1.17 μg/L) and in children with KD were similar (p = 0.569). Patients in the control group suffered from acute infections, including four bacterial infections and one child hospitalized for herpetic gingivostomatitis.The mean mercury was 4.15 ± 0.37 (standard error) μg/L. Of the 79 eligible KD patients, mercury levels in the acute phase prior to administering initial IVIG ranged from 0.4 to 19.4 μg/L, with a median of 3 μg/L. The mercury levels of six KD patients were undetectable. We excluded undetected data in our analysis for the continuous mercury variable  but no statistically significant correlation with leukocyte count, percentage of neutrophil, lymphocyte, monocyte, eosinophil, basophil, platelet count, aspartate transaminase, alanine transaminase, or C reactive protein. However, data failed to reach a significant difference after excluding the child with blood mercury exceeding the toxic value above 15 μg/L. A total of seven children with mercury data were missing blood sodium concentrations. With Pearson’s correlation coefficient, mercury levels showed a strong association with sodium (p > 0.05). No significant difference in the ratio of blood mercury to sodium was observed between the IVIG response and resistant groups.After obtaining a positive finding, we further investigated the association between the ratio of blood mercury to sodium and disease outcome. However, the ratio of blood mercury to sodium between CAL and non-CAL groups failed to reach a significant difference (p = 0.022).The relationship between mercury levels and laboratory data values is presented in n = 14) were obtained from patients with KD before and after treatment with IVIG. The tests revealed no difference in mercury levels between patients with KD before and after IVIG (2.25 (0.775–5.5) μg/L vs. 2.5 (1.20–5.75) μg/L, p = 0.177).Paired blood samples  from one of the National human biomonitoring, followed by the Japanese population in Asahikawa , Korean population , and American population  [han 0.05 .To the best of our knowledge, we are the first to determine blood mercury levels in KD patients and all the patients in this study are from Taiwan. After actually measuring the mercury concentration in KD patients’ blood, we found that mercury concentration was not related to either clinical manifestations or disease prognosis. Presumably, the cause may be that KD patients primarily presented with blood mercury levels < 15 μg/L (98.82%), which are considered normal and subtoxic ,31. HoweThese results suggest that blood mercury levels were negatively correlated with sodium levels. Carter et al. reported a boy with acute mercury toxicity was complicated by hyponatremia . SimilarExposure to environmental toxins like mercury is known to have lasting adverse effects on the cardiovascular system, such as coronary heart disease in adults . HoweverA national survey for mercury concentration in blood suggests the higher levels in Asia, while the population groups from the United States have the lower levels of total mercury, consistent with the high incidence of KD in Japan, Korea, China and Taiwan and its low incidence in North America. Although the instruments used to measure mercury concentration in studies from the United States (ICP-MS), Taiwan (ICP-MS), South Korea , China , and Japan (cold vapor atomic absorption spectrometry) were different, the determination of mercury concentration in fish found by ICP-MS was not significantly different than the one obtained by Direct Mercury Analyzer . The merThe consumption of seafood is important in general Japanese and Taiwanese food, regardless of age. In addition to the fact that fish intake may be a main source of mercury, industrial emissions to the soil’s surface, atmospheric pollution from overseas, distinct living region, age, and races were also considered as factors affecting blood mercury levels . MercuryIn terms of national comparisons, we reported that children in Taiwan displayed the higher concentrations of mercury. This finding highlights the importance of studying blood mercury concentrations in Taiwanese children and also mercury levels in KD patients. Large-scale comprehensive studies are needed to protect children’s health, reduce and avoid mercury exposure.


We have observed that some preterm infants whose fundus appears very similar to eyes with familial exudative vitreoretinopathy (FEVR) present with atypical retinopathy of prematurity (ROP). To establish a definitive diagnosis and explore the possible genetic mechanism of atypical ROP, we performed gene sequencing of these cases using next-generation sequencing technology.  A retrospective review of infants who presented with atypical ROP from October 2013 to February 2017 was performed. The data included gender, gestational age at birth, birth weight, family history, systemic disorders, and age-appropriate ophthalmic examinations. Fundus fluorescein angiography (FFA) of the parents was also performed. Peripheral blood was collected from the patients and their parents to sequence genes. Gene mutations were analysed.  Genetic testing revealed that 9 infants had FEVR-related disease-causing gene mutations. Nine gene mutations were detected; 5 had already been reported, and the other 4 were novel. In the 18 eyes of these 9 patients, 9 eyes exhibited severe ROP. 5 cases had a positive family history. LRP5), frizzled-4(FZD4), Norrie disease protein (NDP), and tetraspanin-12(TSPAN12) may play a role in the pathogenesis of ROP and cause atypical ROP or preterm FEVR. The fundus lesions of ROP patients with disease-causing gene mutations were more serious. ROP cases should be carefully differentiated from preterm FEVR cases. Gene mutations of low-density-lipoprotein receptor-related protein 5( Retinopathy of prematurity (ROP) is a complex retinal vascular disorder, and its phenotype has many similarities with familial exudative vitreoretinopathy (FEVR). Both diseases are based on abnormal development of retinal blood vessels, so there are secondary retinal complications, including retinal folds and detachment. Retinopathy in premature infants can be regarded as the arrest of normal development of retinal nerve and blood vessels, and its final pathological compensatory mechanism leads to abnormal retinal vascularisation . FEVR isTraditionally, when clinical manifestations are difficult to diagnose, the only strategy to distinguish between diseases has been through clinical history. ROP is a disease that occurs in premature infants and generally has no genetic predisposition. However, FEVR tends to be inherited and can be observed in affected infants at full term. In clinical work, we have found a series of atypical ROP cases appearing very similar to FEVR. To confirm the diagnosis and explore the genetic mechanism of atypical ROP, we used second-generation sequencing technology to carry out gene detection in these cases.n = 9) with FEVR-associated mutations.This retrospective study was based on the tenets of the Declaration of Helsinki. Written informed consent was obtained from all patients or their guardians. From October 2013 to February 2017, data were collected for infants who presented with atypical ROP at the Xinhua Hospital Affiliated to Shanghai Jiao Tong University. Next-generation sequencing technology  was used to perform gene sequencing in these cases. We identified a series of ROP patients  at birth, birth weight (BW), dates of fundus fluorescein angiography (FFA), etc. The tests used in the study were performed before treatment.We followed the methods of our team's FEVR-related topic . All proFZD4), low-density-lipoprotein receptor-related protein 5 (LRP5), Norrie disease protein (NDP), tetraspanin-12 (TSPAN12), and zinc finger protein 408 (ZNF408), which are known to be related to FEVR (kinesin family member 11 (KIF11) and the β-catenin gene (CTNNB1) were not screened in this study because of their low incidence in FEVR). The variants previously reported in the Human Gene Mutation Database  were identified as pathogenic. The public databases were used to filter loci with allele frequencies (MAFs) greater than 0.05, and the candidate pathogenic mutations were those that led to a change in the gene structure or an amino acid. The pathogenicity of candidate mutations was evaluated by computer simulation prediction. Then, the criteria of the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines [Peripheral blood samples were collected from all family members who signed the consent from. NGS genetic analysis was carried out on frizzled-4  were stage 1, 3 (16.67%) were stage 4a, 4 (22.22%) were stage 4b, and 6 (33.33%) were stage 5. We defined “severe ROP” as any case at stage 3. Severe ROP developed in 13 eyes (72.22%) .LRP5 and NDP mutations were the most common , followed by mutations in FZD4  and TSPAN12 . All NDP mutations were hemizygous, and the other mutations were heterozygous. At least one computer simulation prediction of each novel variant was “damaging,” “probably damaging,” or “disease-causing,” and the allelic frequency (AF) of these variants was very low (N/A or <0.05) in all databases that we accessed. Therefore, we considered these 3 novel variants (c.2431A > G and c.1434G > A in LRP5 and c.194C > T in TSPAN12) to be likely pathogenic gene mutations. However, obvious ascertainment bias for sporadic cases could not be completely excluded. Further studies to determine the function of these loci are needed to prove this theory.Stage 1 lesions were mostly located in zone 2 without plus disease. As observed in the angiogram, irregular sprouts of vascularisation at the vascular/avascular junction, distinct pruning of vessels, and pinpoint areas of hyperfluorescence were observed . In addiNDP mutations were paternally inherited. Of the other mutations, four were maternally inherited, and two were paternally inherited.Of the 9 patients, 5 (55.56%) had a positive family history. All patients had no bone, hearing, or other anomalies except for prematurity.LRP5, FZD4, TSPAN12, NDP, and ZNF408. FEVR has Mendelian inheritance [The characteristic of FEVR is failure of peripheral retinal vascularisation during ophthalmic development, which is associated with a spectrum of clinical manifestations. FEVR can be confirmed by genetic testing . To dateeritance –14. ROP Recently, several genetic analyses have shown that FEVR-related mutations exist in children with advanced ROP –21. The Some scholars believe that most ROP patients display high-fluorescence lesions similar to “popcorn,” abnormal branches , local telangiectasis, neovascularisation, and leakage . HoweverAll nine cases except for two (cases 1 and 2) had a GA of 34 weeks or more and a minimum BW of 2200 grams. China's ROP screening standards are a BW < 2000 grams and a GA < 32 weeks. The GAs and BWs of these seven infants were significantly greater than those of the infants with typical ROP. Furthermore, in four cases , the GAs were 36 weeks, which is close to full term. Vascularisation of the retina begins at approximately 18 weeks of gestation and is complete by 38–40 weeks of gestation . ROP repCase 1 was born at a GA of 29 weeks with a BW of 1050 g, and both eyes were zone II stage 1 without plus disease. The case was not serious, and according to the characteristics of FFA, we considered this case to be similar to FEVR. Case 2 was born at a GA of 28 weeks with a BW of 1270 g. Both eyes were stage 4a with temporal tractional retinal detachment, proliferation, exudation, and macular dragging. This case is more similar to a typical ROP.FZD4 gene were found in up to 7.5% of patients with severe ROP [FZD4 double missense mutation and both ROP and FEVR [FZD4 or LRP5 [NDP gene [TSPAN12 gene in a patient with threshold ROP [John  reportedvere ROP –41. A st or LRP5 . AccordiNDP gene . These sNDP gene . Recentlhold ROP . HoweverROP cases should be carefully differentiated from preterm FEVR cases, especially ROPER and preterm FEVR. However, distinguishing the two diseases only by GA is unreasonable. ROPER presents with indeterminate activation episodes, and FEVR is relatively stable; accurate diagnosis provides guiding significance for treatment. ROPER requires close monitoring for disease progression early and often throughout life, including serial FA and treatment with cryotherapy, laser, and anti–vascular endothelial growth factor (anti-VEGF) injections . HoweverLRP5, FZD4, NDP, and TSPAN12 may play a role in the pathogenesis of ROP and cause atypical ROP or preterm FEVR. The fundus lesions of ROP patients with disease-causing gene mutations are more serious and may be FEVR combined with ROP, and such diseases may be called ROPER. ROP cases should be carefully differentiated from preterm FEVR cases.ROP is a complex disease in that evidence suggests that it is influenced by both genetic and environmental factors. Our findings showed that gene mutations of


Immediately before stenting and at completion of pPCI, IMR was measured within the infarct related artery (IRA). At the same time points, 2 angiographic views were acquired during hyperaemia to measure quantitative flow ratio (QFR) from which IMRangio was derived. In a subset of 15 patients both IMR and IMRangio were also measured in the non-IRA. Patients underwent cardiovascular magnetic resonance imaging (CMR) at 48 h for assessment of microvascular obstruction (MVO). IMRangio and IMR were significantly correlated . Both IMR and IMRangio were higher in the IRA rather than in the non-IRA  and were higher in patients with evidence of clinically significant MVO (> 1.55% of left ventricular mass) . Post-pPCI IMRangio presented and area under the curve (AUC) of 0.96  for prediction of post-pPCI IMR > 40U and of 0.81  for MVO > 1.55%. IMRangio is a promising tool for the assessment of coronary microcirculation. Assessment of IMR without the use of a pressure-wire may enable more rapid, convenient and cost-effective assessment of coronary microvascular function.Immediate assessment of coronary microcirculation during treatment of ST elevation myocardial infarction (STEMI) may facilitate patient stratification for targeted treatment algorithms. Use of pressure-wire to measure the index of microcirculatory resistance (IMR) is possible but has inevitable practical restrictions. We aimed to develop and validate angiography-derived index of microcirculatory resistance (IMRThe online version of this article (10.1007/s10554-020-01831-7) contains supplementary material, which is available to authorized users. Coronary microvascular injury remains an important determinant of poor prognosis and an unsolved challenge in the management of patients with ST elevation myocardial infarction (STEMI). The index of microcirculatory resistance (IMR) has been proposed to provide information about the status of coronary microvasculature and it is based on the combined application of thermodilution technique and of coronary pressure-wire . It has Despite encouraging preliminary results of studies showing the potential efficacy of IMR-guidance in triaging novel therapies in STEMI , IMR is Quantitative flow ratio (QFR) is a novel angiography-based index derived from application of computational flow dynamics to three-dimensional modelling of the coronary artery . QFR hasangio), to provide a pressure-wire-free alternative to IMR for the assessment of coronary microvasculature.By measuring QFR in the IRA, we aimed to derive and validate a novel index, the angiography-derived index of microcirculatory resistance  study. Details about OxAMI study have been previously described . The OxAangio and IMR assessment in case of haemodynamic instability, evidence of angiographic left main disease, anticipated plain old balloon angioplasty without stent implantation or unsuitability for CMR assessment.STEMI was defined as the occurrence of ongoing chest pain for at least 30 min associated with ST-segment elevation > 2 mm in at least two contiguous leads. Enrolled patients were excluded for IMRFigure IMR was measured using thermodilution technique on the CoroFlow system  as previously described, immediately before stenting and at completion of pPCI . Brieflywhen assessed before stenting, IMR was measured either according to the above formula and also corrected for coronary wedge pressure, to account for residual collateral flow:Coronary wedge pressure was measured by the pressure sensor of the pressure-wire during prolonged angioplasty-balloon inflation.In a subset of patients, IMR was measured also in one of the two non-IRAs. The selection of which non-IRA to assess was left to operator’s discretion.At the same time points when IMR was measured, and only when measurement of IMR was completed, angiographic images were acquired at 15 frame/second with manual injection of contrast dye during maximal hyperaemia, using a monoplane radiographic system . Pre-specified projections were agreed with the radiographer to guarantee views at least 25° apart.Three-dimensional quantitative coronary angiography (3D-QCA) and then QFR were measured off-line using QAngio® XA 3D software  by two independent operators  blinded to clinical, IMR and CMR data. Contrast-flow QFR (cQFR) and fixed-flow QFR (fQFR) were provided. Cases of disagreement were resolved by consensus.angio under hyperaemic conditions, as well. For this reason, QFR was assessed using the angiographic views taken at peak hyperaemia during adenosine infusion. Pressure-wire was left in place during angiographic acquisition to allow calculation of QFR exactly at the site of the distal pressure/temperature transducer.Since IMR is measured during maximal hyperaemia, we elected to assess IMRAs per IMR, in a subset of patients, QFR was measured also in one of the two non-IRAs.angio was derived starting from the formula for calculation of IMR.(hyperaemia) is distal pressure at hyperaemia and tTmean(hyperaemia) is mean transit time at hyperaemia. By multiplying and dividing by hyperaemic aortic pressure (Pa(hyperaemia)), the formula becomes:IMR(hyperaemia) can be expressed as the ratio between the number of frames (Nframes) for contrast dye to travel, during hyperaemia, from the guiding catheter to a distal reference  divided by the acquisition rate (fps).Since QFR is a surrogate of Pd(hyperaemia)/Pa(hyperaemia) ratio, . Sequence acquisition was performed as previously described .Microvascular obstruction (MVO) was defined as hypointense area within the hyperenhancement region on the late gadolinium enhancement images and was manually contoured . We consAfter verifying normal distribution by Shapiro–Wilk’s test, variables were expressed as mean and ( ±) standard deviation (SD) or as median accompanied by interquartile range (IQR), as appropriate. Frequencies were compared using Chi square test or Fisher’s exact test, as appropriate. Continuous variables were compared using T test or analysis of variance (ANOVA) with Scheffe’s post-hoc comparisons, as appropriate. Non-normally distributed continuous variables were compared using Mann–Whitney’s test or Kruskall Wallis’ test, as appropriate. T test or Wilcoxon test were used as appropriate for paired samples. Correlations between variables were expressed using Pearson r or Spearman rho coefficients as appropriate.Inter-rater reliability was assessed by interclass coefficient (ICC) and corresponding 95% confidence interval.angio and IMR was assessed by Bland–Altman plot and the diagnostic efficiency of IMRangio in predicting IMR ≥ 40U and MVO > 1.55% was assessed by the area under the receiver-operating characteristic curve. Youden index analysis was used to identify best cut-off of IMRangio for prediction of post-pPCI IMR ≥ 40U.The concordance between IMRStatistical analysis was performed using SPSS 24.0  and a p value < 0.05 was considered statistically significant.angio above or below 40 U (Supplementary Table 1 and 2). The cut-off of 40U for IMRangio was derived from ROC analysis , F = 14.02, p < 0.001).Satisfactory inter-rater reliability was detected for QFR (ICC 0.83 (CI95% 0.61–0.93), F = 6.37, p < 0.001) and IMRGood correlation was observed between FFR and QFR .angio were significantly correlated in the overall sample of 92 lesions  . Correlation between the two variables was maintained when analysis was restricted to only IRA pre-pPCI , IRA post-pPCI  and to the non-IRA  .Pre-pPCI IMRangio and IMR were significantly lower in the non-IRA compared to IRA (IMRangio = 17.8U (12.2–29.9) vs 30.0U (20.5–44.3), p = 0.006; IMR = 19.0U (12.5–27.5) vs 31.0 (16.8–55.2), p = 0.01) .Notably, both IMRangio in predicting an IMR ≥ 40 U .ROC curve analysis showed an excellent diagnostic performance of IMRangio within the whole sample and across subgroups  .Bland Altman analysis further confirmed concordance between IMRRA) Fig. . Only seangio and IMR before and after stenting was available in 33 out of 45 patients. Both IMRangio and IMR decreased significantly after stenting in the IRA (IMRangio from 40.7U (25.0–50.2) to 28.2 (20.2–41.7), p = 0.048; IMR from 48.6U (25.5–64.4) to 31.0 (16.9–51.7), p = 0.048)  to 21.3U (14.9–31.7) (p = 0.002) and IMR from 41.9U (22.6–58.9) to 20.3U (15.0–28.0) (p = 0.001). In partial/poor responders IMRangio went from 44.3U (25.0–57.6) to 44.8U (41.2–64.3) (p = 0.18) and IMR from 57.5U (34.4–102.8) to 66.2U (43.1–105.9) (p = 0.21). Using the threshold of 40U, post-pPCI IMR categorized 63.6% of patients as good responders, whilst post-pPCI IMRangio categorized 69.7% of patients as good responders (p = 0.69). IMRangio presented a 3% misclassification rate for response to stenting, with only 1 out of the 33 patients misclassified as “good responder” by IMRangio and labelled as “poor responder” according to IMR variation post pPCI.Assessment of both IMRangio above or below 40U.CMR data are summarised in Table angio was significantly higher in patients with MVO > 1.55% (48.1U (29.3–68.9) vs 22.6U (13.7–39.0), p = 0.005). Post-pPCI IMRangio presented a satisfactory efficiency for prediction of MVO > 1.55% (AUC = 0.81 (CI95% 0.65–0.97), p = 0.006) .IMR.1U 29.3–8.9 vs 22angio as a novel and pressure-wire-free index for the assessment of coronary microcirculation in STEMI patients. We have specifically observed that:angio is significantly correlated with IMR both in the IRA and in the non-IRA of STEMI patientsIMRangio are significantly higher in the IRA than in the non-IRABoth IMR and IMRangio to predict an abnormal IMR (≥ 40 U) in STEMI patientsA value of 40 U appears the best threshold of IMRangio and IMR is maintained when these variables are measured before or after pPCIThe correlation between IMRangio variation before and after pPCI mirrors the same variation that is observed in IMRIMRangio measured at the end of pPCI is higher in patients with significant MVO and can predict the occurrence of significant MVO (> 1.55% of left ventricle mass).IMRIn the current study, we have derived and validated IMRThe availability and performance of pPCI have changed the prognosis for patients presenting with STEMI. However, up to 25–33% of STEMI patients will develop heart failure within five years of treatment, despite contemporary therapy . ExtensiIn addressing this challenge, assessing the status of coronary microvasculature within the catheter laboratory at the time of STEMI is pivotal since it has the potential to triage patients who might benefit from additional therapy. Early diagnosis/identification of “high risk’ individuals is essential and IMR measurement using pressure-wire can offer a reasonable compromise between practicality and diagnostic accuracy. However, measuring IMR increases procedural time, cost and has an intrinsic  risk related to additional wire manipulation of the IRA Fig. .Fig. 7PoWithin routine interventional practice, novel angiography-based indices are becoming available to address the limitations of pressure-wire-based measurement of FFR, using computational flow dynamics to model the coronary artery . Amongstangio, can be measured in STEMI patients in the vast majority of cases in a standard catheter laboratory . Comparisons showed a significant correlation between IMR and IMRangio, as confirmed by the ROC curve analysis. Previously, a post-pPCI IMR ≥ 40U has been shown to be prognostically relevant [angio showed a similar upper cut-off of 40U to predict abnormal IMR. When applying this threshold of 40U for both IMR and IMRangio, they were concordant in 92% of cases, especially when the assessment was performed at the end of pPCI or in the non-IRA compared to assessment in the IRA before stent implant.This study demonstrates that IMR derived from QFR, labelled as IMRrelevant  and notaangio and IMR are not numerically different for IMR values below 75U. Above 75U, IMRangio can be instead either higher or lower than IMR. This observation emphasises that the absolute numerical values of the two variables are less related in cases of extreme (very high IMR) microvascular dysfunction  in cases of extreme microvascular dysfunction, with no cases of severely abnormal IMR presenting a normal IMRangio and vice versa. Notably, the few cases of discordance were clustered around the threshold of 40U . We have previously described that, overall, IMR tends to improve after stenting, as a consequence of flow-mediated dilation of the microvascular bed angio in this study, with a similar rate of poor or partial responders to stenting when classification was based either on final IMRangio or IMR.In our study IMR and IMRangio appeared significantly elevated in patients with evidence of clinically significant MVO (> 1.55% of left ventricle mass) on CMR. This observation echoes that by McGeoch et al. who reported higher IMR values in STEMI patients with MVO Recently de Waha et al. have reported, in a pooled cohort of 1688 STEMI patients undergoing post-pPCI CMR, that MVO > 1.55% of left ventricle mass was associated with higher rates of mortality and heart failure at one year angio were correlated with the presence of MVO, neither of them presented a strong correlation with the extent of MVO and infarct size. This discrepancy is consistent with previous studies angio measurement and CMR scanning and the fact that IMR/ IMRangio provides a functional assessment of coronary microcirculatory injury, whilst CMR an anatomical one Notably, whilst IMR and IMRThe relatively small sample size represents a limiting factor to keep into account when interpreting the results of the current study.angio were both measured offline. This accounts for a small proportion of lesions that had to be discarded for IMRangio assessment because of suboptimal quality of angiographic views.A second observation is that QFR and IMRangio), was derived from angiographic views acquired at maximal hyperaemia achieved during intravenous adenosine infusion. In fact, the assessment of microvascular function in STEMI appears to be more reliable and consistent at maximal hyperaemia, since it is less prone to the heterogeneity of the same measurements obtained under resting conditions One of the advocated benefits of QFR in management of patients with stable coronary disease is that accuracy is maintained in predicting FFR, irrespective of the use of adenosine to achieve maximal vasodilation. The so called “contrast-QFR” represents an index that is pressure-wire and adenosine-free . In our angio might maintain the same diagnostic accuracy in predicting IMR and MVO also under non-hyperaemic conditions needs to be evaluated in future studies.Whether IMRangio is a pressure-wire-free index with the potential to provide an easier and routine assessment of coronary microcirculation in the emergency setting of STEMI. Ultimately, even though further prospective validation is necessary in STEMI and across the spectrum of coronary artery disease, IMRangio can be an easy, quick and cost-effective point-of-care test for routine assessment of microvascular function in the catheter lab with the ultimate goal of facilitating prognostic stratification and early triage of ad-hoc/personalised therapies.IMRSupplementary file1 (DOCX 220 kb)Below is the link to the electronic supplementary material.


Laparoscopic resections for rectal cancer are routinely performed in high-volume centres. Despite short-term advantages have been demonstrated, the oncological outcomes are still debated. The aim of this study was to compare the oncological adequateness of the surgical specimen and the long-term outcomes between open (ORR) and laparoscopic (LRR) rectal resections.Patients undergoing laparoscopic or open rectal resections from January 1, 2013, to December 31, 2019, were enrolled. A 1:2 propensity score matching was performed according to age, sex, BMI, ASA score, comorbidities, distance from the anal verge, and clinical T and N stage.p = 0.567) and postoperative morbidity . LRR group had a significantly earlier soft oral intake (p < 0.001), first bowel movement (p < 0.001), and shorter hospital stay (p < 0.001). Oncological adequateness was achieved in 85 (86.7%) open and 44 (88.0%) laparoscopic resections (p = 0.772). Clearance of the distal  and radial margins , and mesorectal integrity  were comparable between groups. No differences in local recurrence , 3-year overall survival , and disease-free survival  were observed.Ninety-eight ORR were matched to 50 LRR. No differences were observed in terms of operative time (224.9 min. vs. 230.7; LRR is associated with good postoperative results, safe oncological adequateness of the surgical specimen, and comparable survivals to open surgery. Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth cause of cancer-related deaths. About 35% of CRC are localized in the rectum . NowadayIn an effort to minimize the impact of surgery, minimally invasive techniques such as laparoscopy and robotics have been implemented in the last 30 years. In this setting, laparoscopic resection for right and left colon cancer has been associated with better short-term outcomes and similar survivals as compared to open –12. NotwDue to the lack of consensus, the aim of this study was to compare laparoscopic and open resections for rectal cancer in terms of the oncological adequateness of the surgical specimen and to evaluate the perioperative and oncological outcomes.All consecutive patients undergoing surgery for rectal cancer at the General Surgery Department of Sant’Andrea University Hospital from January 1, 2013, to December 31, 2019, were included in this study. Data were retrospectively reviewed from a prospectively maintained database including demographics, tumour characteristics, operative details, tumour pathology, and short- and long-term outcomes. All patients aged 18 or older, with a histological diagnosis of adenocarcinoma of the rectum within 15 cm from the anal verge who underwent a rectal resection, were included in the study. Early rectal cancers treated by endoscopic resection, transanal endoscopic microsurgery (TEM), or transanal minimally invasive surgery (TAMIS); advanced cancers invading surrounding structures, metachronous tumours, metastatic cancers requiring major hepatectomies or more than two metastasectomies; patients with a single hepatic metastasis larger than 4 cm as well as patients with other abdominal malignancies were excluded. Patients were then divided into two groups according to the surgical approach: laparoscopic (LRR group) and open (ORR group)  or endorectal ultrasound in all patients and a total body CT scan was performed in order to detect distant metastases.Cancers were defined as high (10–15 cm), middle (5–10 cm), or low (0–5 cm) rectal tumours according to the distance from the anal verge. Surgical specimens were examined by a single pathologist (E.P). These were received fresh and opened on the anterior wall from the proximal margin up to 4 cm above the peritoneal reflection for fixation. Before sampling, the integrity of the mesorectum was assessed and the circumferential margin below the peritoneum was inked Fig. . The speMorbidity and mortality were defined as postoperative complications and death within 30 days from surgery respectively. Morbidity was graded according to the Clavien-Dindo classification and complications graded > II were defined as major .Overall survival (OS) was defined as the time between surgery and death for any cause or last follow-up. Disease-free survival (DFS) was defined as the time from the operation to tumour recurrence either local or distant.Neoadjuvant long- or short-course chemo-radiotherapy and adjuvant chemotherapy were administered according to the guidelines of the Italian Society of Medical Oncology (AIOM).Open procedures were performed through a midline laparotomy while a 3 to 4 trocar technique with Pfannesteil incision for the specimen extraction was used in the laparoscopic group. A central ligation of the inferior mesenteric vessels was carried out in both open and laparoscopic cases and the splenic colonic flexure was always taken down. The lateral-to-medial technique was usually preferred in open procedures, whereas medial-to-lateral was more often chosen in laparoscopic surgeries. All the procedures were performed respecting the principles of the total mesorectal excision (TME) . Partialt test was used to compare differences in continuous parametric variables and the Mann-Whitney U test for continuous non-parametric variables. Numbers and percentages were used for reporting categorical variables and the χ2 test was used for comparisons. A propensity score matching was applied to eliminate selection bias between groups and reported according to the recommendations of Lonjon et al. [Continuous data were expressed as the mean (± standard deviation) or median and interquartile range depending on their distribution that was assessed through the Shapiro-Wilk test. An unpaired Student n et al.  Variablep value less than 0.05. Statistical analysis was performed using the SPSS software 25.0 .Survival analyses were conducted using the Kaplan-Meier method with log-rank test comparisons. Significance was defined as a Between January 2013 and December 2019, a total of 318 patients underwent a rectal resection for a histologically proven adenocarcinoma at our institution. Three patients who underwent TEM, 6 TAMIS, 54 endoscopic resections, 15 resections of surrounding structures (cT4b), 5 metachronous colonic resections, 3 major liver resections, 10 multiple hepatic wedge resections, 3 metastasectomies larger than 4 cm, and 2 concomitant resections of other abdominal malignancies were excluded from the study. Finally, 217 patients fulfilled the study criteria and were therefore included. One hundred fifty-three (70.5%) patients underwent an open rectal resection while 64 (29.5%) were operated on by laparoscopy.p = 0.641). Larger tumours were operated in the open group compared to laparoscopy  while preoperative clinical staging was comparable both in terms of T and N stage (Table p = 0.36). Finally, more patients in the ORR group underwent concomitant surgical procedures   and a diverting ostomy was chosen in 57 (58.1%) open and 23 (46%) laparoscopic patients (p = 0.34). Postoperative outcomes are depicted in Table p < 0.001), as well as time to first bowel movement  and time to soft oral intake . Morbidity was similar between groups  with most of the complications being minor according to the Clavien-Dindo classification (14.4% in ORR vs. 8.3% in LRR p = 0.40). Finally, the length of hospital stay was significantly shorter in the laparoscopic group .After propensity score matching, 98 ORR were compared to 50 LRR. Anterior rectal resection was the most common type of operation performed in both groups , TNM stage (p = 0.96), number of retrieved lymph nodes  as well as number of positive nodes between groups. Furthermore, R0 resection was achieved in 89.8% and 90% of cases in LRR and ORR respectively (p = 0.56). Oncological adequateness of the resected specimen was confirmed in 86.7% ORR and in 88.0% LRR with no significant differences (p = 0.772). In detail, the distal margin was clear for almost every resection both in open and laparoscopy , whereas the circumferential margin was negative in 91.8% ORR and 90% LRR (p = 0.70). Finally, complete mesorectal integrity was achieved in 94.9% ORR and in 98% LRR (p = 0.365).Pathological examination of the resected specimen showed comparable sizes of the tumour . The 3-year actuarial DFS rate was 73.1% in ORR and 74.3% in LRR  months, the 3-year actuarial OS rate was 82.9% for open and 91.4% for laparoscopy (p = 0.37).Two subgroups were further analysed according to the location of the tumour below the peritoneal reflection: the middle rectum group  and the low rectum group . Patients in both groups underwent a total mesorectal excision and the oncological adequateness of the resection of middle versus low rectal tumours was comparable regardless of the surgical technique  and in the low rectum group . Furthermore, no statistically significant differences were observed between ORR and LRR patients regarding the distal and circumferential clearance and mesorectal integrity for both middle and low rectum groups  or in which an associated major procedure is preoperatively planned (i.e. metastatic disease requiring contemporary liver resections). Notwithstanding, we still matched the groups using propensity score analysis to correct for undetectable selection bias eventually improving the statistical power of the study.This study has some limitations mainly being the retrospective fashion and the relatively small sample size. The study was limited to the most recent 5-year period to avoid bias induced by the learning curve effect. Indeed, in 2013, the 4 surgeons were already all experienced in the laparoscopic colon and rectal resections reducing the bias of surgical technique. Furthermore, they independently performed both open and laparoscopic procedures.Laparoscopic surgery for rectal cancer is associated with good postoperative results. Compared to the open approach, oncological adequateness of the resected specimen is respected, even in the setting of middle and low rectal tumours eventually ensuring long-term survivals. Surgeons in high-volume centres should be encouraged to perform more laparoscopic resections in order to provide improved postoperative recovery maintaining safe long-term survival.


Atelectasis is a common side effect of general anesthesia. Prevention of lung atelectasis, carbon dioxide retention, and chest infection would improve the quality of medical care and decrease hospital stay and costs. The aim of this study was to compare the effects of volume-controlled ventilation (VCV) and pressure-controlled volume-guaranteed ventilation (PCVG) on postoperative lung atelectasis using lung ultrasound (LUS) following upper abdominal laparotomies.n = 30): received intraoperative volume-controlled ventilation (VCV) mode and group (n = 30): received intraoperative pressure-controlled ventilation volume-guaranteed (PCV-VG) mode. Arterial blood samples were obtained immediately after extubation, and 30, 120, 240, and 360 min postextubation. Lung ultrasound was done intraoperatively at 30 min from induction, immediate, and 120 and after 360 min postoperatively. There was difference between two groups favoring PCV-VG group but that difference failed to be statically significant regarding arterial partial pressure of oxygen (PaO2) and arterial carbon dioxide tension (PaCo2) between the two groups in preoperative, immediate postoperative, and 120, 240, and 360 min postoperative. Arterial oxygen saturation (SaO2) was significantly lower among patients in the VCV group immediate postextubation compared with patients in group PCV-VG . Although signs of atelectasis were low in group B, 36.7% of the patients showed normal lung ultrasound, 63.3% showed various abnormalities, 46.7% showed the presence of lung pulse , and 46.7% showed B lines , while 30% of the patients showed the absence of A-lines . Also, some patients demonstrated more than one sign. However, there was no a significant difference between the two groups both showed atelectasis immediate, 2 h and 6 h postoperatively.Sixty patients  scheduled for upper abdominal laparotomies. They were randomly allocated into two equal groups: Group A (PCV-VG offered no significant advantage over VCV regarding the occurrence of the postoperative atelectasis. However, we prefer to use PCV-VG as postoperative hypoxia and atelectasis was much less in that mode. Further, large-scale studies are required to confirm these findings and to establish a definite conclusion. General anesthesia causes depression in both respiratory centers and respiratory muscles. Hence, patients under general anesthesia require adequate ventilatory support to maintain arterial oxygenation and eliminate carbon dioxide  is the most commonly used modes. In this mode, a preset tidal volume (TV) with a constant flow during the preset inspiratory time (Ti) at the preset respiratory rate is delivered with each breath. The disadvantages of VCV include a higher airway pressure at the end of inspiration than during pressure-controlled ventilation (PCV)  is the early signs of atelectasis. With progressive absorption of air, there is a loss of volume leading to a hypoechoic pattern known as static air Broncho gram (late sign) : received intraoperative volume controlled ventilation (VCV) mode and group B (n=30): received intraoperative pressure controlled ventilation – volume guaranteed (PCV- VG) mode.After approval of the Research Ethical Committee of the Faculty of Medicine, Ain Shams University, and obtaining informed consent, this prospective randomized comparative study was conducted in Ain Shams University Hospitals. Sixty patients  scheduled for upper abdominal laparotomies lasting 3 to 6 h were included in this study. They were randomly allocated into two equal groups using computer-generated randomized table and sealed opaque envelopes. Group A  preoperative PaCOPatients who refused to participate in the study, those who had pulmonary, severe hepatic, cardiac or renal diseases, or had body mass index (BMI) more than 25, a position rather than supine or a duration less than 3 h were excluded from the study. If any of the patients experienced hemodynamic instability such as massive hemorrhage, he/she was omitted from study.2, PaO2, and SaO2 were obtained, and baseline lung ultrasound was performed before the operation.Patients underwent a thorough preoperative assessment including a detailed history, physical examination, laboratory investigations, and chest X-ray evaluation. All patients included in the study were fasting for at least 8 h before the induction of anesthesia. Baseline arterial blood gases (ABG) for PaCOPatients received 0.02 mg/kg intravenous (IV) midazolam as premedication. Prophylaxis for postoperative nausea and vomiting included intravenous ondansetron (4 mg). In the operating room (OR), standard monitoring in the form of a five-lead electrocardiogram, noninvasive blood pressure, pulse oximetry, and capnography were established.Induction of anesthesia was done by preoxygenation followed by 1–2 mg/kg IV propofol, 1–2 μg/kg IV fentanyl, 0.5 mg/kg IV atracurium to facilitate tracheal intubation. Maintenance of anesthesia was achieved by 0.5–1 MAC of isoflurane in a 50% oxygen/air mixture and 0.15 mg/kg IV atracurium boluses guided by a nerve stimulator, and the patients received fluid requirements. Fluid intake was in the form of crystalloid.2 32-35 mmHg) and well oxygenation I to E ratio set at 1:2 and P max at 40 cm H2O. A positive-end expiratory pressure (PEEP) of 5 cm H2O was added in both modes throughout the surgery. FiO2 was 0.6 throughout the whole operation. In the VCV group, the ventilator settings were continued throughout the study. In the PCV-VG group, PCV-VG mode was chosen to achieve VT 6–8 mL/kg, with RR adjusted to maintain ETCO2 32–35 mmHg. Intraoperative LUS was performed 30 min after induction. Recovery was carried out after closure of the surgical wound by turning off isoflurane vaporizer and increasing FiO2 to 1.0. When respiratory attempts started, neostigmine (0.02–0.04 mg/kg) and atropine (0.02 mg/kg) were given to reverse residual neuromuscular block. This was followed by extubation when awake and patient transferal to Post-Anesthesia Care Unit (PACU). The patients were put in the semi-setting position at the PACU with supplementation of oxygen face mask, and then, the patient was discharged to the ward after fulfilling the recovery criteria. Postoperative analgesia was provided to keep patients with a visual analog scale (VAS) less than 3 in the form of paracetamol (10–15 mg/kg/6 h) and morphine sulfate (0.05–0.1 mg/kg/Iv) every 6 h. If VAS > 4, top-up doses of morphine were given with max dose 5 mg/6 h for all patients. Arterial blood samples were withdrawn to measure PaCO2, PaO2, and SaO2 immediately after extubation. ABG analysis was also obtained at 120, 240, and 360 min postextubation.All patients were mechanically ventilated using Datex-Omeda ventilator, VCV, or PCV-VG mode according to the allocated group throughout the surgery with a TV of 6–8 ml/kg of ideal body weight, and the respiratory rate was adjusted to maintain normocapnia . Considering a non-inferiority study with a margin of non-inferiority, we estimated that 30 patients in each group were needed to demonstrate a statistically significant difference with a total number of 60 patients. The effect size equals 0.11 .Using the PASS program, settling alpha error at 0.05 and power at 80% results from previous study  as appropriate. Values of pre- and postassessments were analyzed by paired t test or Wilcoxon signed-rank test as appropriate. Chi-square test used to examine the relation between qualitative variables. The confidence interval was set to 95%, and the margin of error accepted was set to 5%. So, the p value was considered significant if < 0.05.Data was analyzed using SPSS win statistical package version 20 . Numerical data were expressed as mean and standard deviation or median and range as appropriate. Qualitative data were expressed as frequency and percentage. For quantitative data, the comparison between two groups was done using either student Seventy-five patients were screened for this study, 10 patients did not meet inclusion criteria and 5 patients refused to participate in our study. The remaining 60 patients were randomly allocated to the groups of the study  and after 30 min  (Table There was no significant difference in SaO7) Table  Fig. 2)2 between2 between the two groups although PaCO2 was lower in the PCVVG group but fail to be statically significant -measured lung aeration has been the gold standard for the study of perioperative atelectasis. However, cumulative radiation exposure and the need to transport the patient to or from the radiology department limit its use even in the research setting  as it enables not only the diagnosis at the patient’s bedside, but also the treatment response assessment in real time  physical status classes I–II, and the surgical procedure was expected to take 2 h. The accuracy of LUS in detecting perioperative atelectasis was compared with thoracic CT as a gold standard. In patients in the supine position, the LUS provides a fast, reliable, and radiation-free method to identify perioperative atelectasis in adults  and a specificity of 89%  for the diagnosis of anesthesia-induced atelectasis  when comparing 36 patients undergoing lumbar spine surgery in the prone position . The study showed that in agreement with our study, no significant differences were reported as regards the ABG analysis, oxygenation, and hemodynamic data between both groups. This could be explained by the issue stated that ERV improves oxygenation through increasing P mean only when alveoli are recruitable, and P mean which is considered a major determinant of arterial oxygenation did not record a significant difference between the studied groups  > 30 kg/mP mean  and group 2 (VCV) . Patients in the last two studies were in similar criteria as our study patients with good respiratory function test results  in the lateral decubitus position. The subjects received various modes of ventilation in random sequences during surgery, including VCV and PCV-VG. No difference in arterial oxygen tension was noted between the groups  to VCV and showed that there was no statistically significant difference in PaO2 values increased significantly after lung inflation in the two groups comparably, but it was still significantly higher in the PCV-VG group   although signs were less in PCV-VG but failed to reach statically significant results.Another study was done using a CT scan as a tool for detecting postoperative lung atelectasis, EL-RAWAS et al., in which 60 obese patients with normal preoperative pulmonary functions scheduled for upper abdominal laparotomies were randomized into two groups. Those in group A received VCV and those in group B received PCV-VG. Arterial blood gases (ABG) were obtained pre-, intra-, and postoperatively. Peak expiratory flow rate (PEFR) and CT chest were done pre- and postoperatively. There was no difference between the two groups as regards the occurrence of postoperative atelectasis. All preoperative CTs were free of atelectasis and the same number of patients developed postoperative basal lung atelectasis in both modes  to VCV in 10 patients with acute lung injury or ARDS, the CT chest showed that like in El Rawas et al. study, surface areas of the basal non-aerated zones were similar in the two modes; however, Prella et al. found that at the apex level, there was a significantly greater non-aerated area in VCV , this may be due to different age groups showing senile emphysema compared to VCV, and PCV-VG seems to provide homogeneous ventilation and better lung aeration in the left and anterior compartments also different position lateral rather than supine position  (Kim et al., Our investigation presents some limitations, which need to be considered. Those limitations may have resulted in these negative findings; first, our study included patients with no lung pathology and has American Society of Anesthesiologist physical statuses I and II; therefore, our results apply only to healthy patients. In respiratory-compromised patients, the results of PCV-VG or VCV may show significant differences. Second, our study did not enroll any morbid obese patients which are a key factor in cardiorespiratory compromise developing in upper laparotomies. Third, our study was done on small numbers of patients which may be responsible for no clinical significant ratio. Moreover, we did not provide any guidance or solution when LUS was assessed to be positive for lung atelectasis and how to prevent it in the perioperative period.PCV-VG offered no significant advantage over VCV regarding the occurrence of the postoperative atelectasis. Further studies are required to determine the effect of each mode of ventilation on respiratory mechanics in different types of patients like obese patients, elder patients, large number, and patients with respiratory diseases. But, we prefer to use PCV-VG as postoperative hypoxia and atelectasis are much less in that mode. Further, large-scale studies are required to confirm these findings and to establish a definite conclusion.


Mycobacterium smegmatis phages Jung and Ronan, isolated from soil in Las Vegas, Nevada. The phages were isolated and annotated by students enrolled in a course for undergraduate research experience (CURE). Jung is a cluster P1 mycobacteriophage, while Ronan is in cluster C1.We present the complete genome sequences of  Mycobacterium smegmatis phages Jung and Ronan, isolated from soil in Las Vegas, Nevada. The phages were isolated and annotated by students enrolled in a course for undergraduate research experience (CURE). Jung is a cluster P1 mycobacteriophage, while Ronan is in cluster C1.We present the complete genome sequences of  Mycobacterium smegmatis is a popular tool for courses for undergraduate research experience (CURE), such as the Howard Hughes Medical Institute’s (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program, on account of its nonpathogenicity, versatility, and ease of cultivation  at the University of Nevada, Las Vegas (UNLV). This was the third time the Phage Discovery course was offered at UNLV; five M. smegmatis phages have been annotated and published from the two previous offerings of the course . The phages were purified and amplified in M. smegmatismc2155. M. smegmatis mc2155 was grown in Middlebrook 7H9 liquid and agar plates at 37°C as described in the Phage Discovery Guide. Liquid cultures were incubated in a tabletop shaker (37°C). Phages were purified by picking plaques with sterile pipettor tips added to 100 μl of phage buffer followed by 10-fold serial dilutions; 10 μl of each dilution was added to 500 μl of bacterial culture and sat undisturbed for 10 min at room temperature. After the addition of 4.0 ml of top agar, the solution was poured evenly over the 7H9 agar plate. Plaque size, morphology, and titer (PFU/ml) were noted after each purification round. The phage was considered purified after three rounds, producing a consistent plaque size and morphology with no sign of bacterial contamination.The phages were isolated in September 2019 from garden soil from UNLV Community Gardens by students enrolled in the BIOL 207 course. Environmental samples were incubated with enrichment broth and shaken  at room temperature, followed by centrifugation and filter sterilization (0.22-μm filter) of the supernatant as specified in the HHMI SEA-PHAGES Phage Discovery Guide . Phage DNA was sequenced at the University of Pittsburgh. Sequencing libraries were prepared from genomic DNA using the NEB Ultra II kit. Libraries were sequenced with an Illumina MiSeq system, producing 150-bp single-end reads sufficient to provide 1,084× coverage for Jung and 273× coverage for Ronan. The reads were quality trimmed and assembled PhagesDB.org database and the Phamerator software with default settings  are listed in settings , 8. Despsettings , while Rhttps://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins), batch CD-Search (https://ncbi.nlm.nih.gov/Structure/bwrpsb/bwrpsb.cgi), and HHPred (https://toolkit.tuebingen.mpg.de/tools/hhpred) with default settings. Using a cutoff E value of 1e-7, we assigned putative functions to 37 genes in Jung (48%) and 67 non-tRNA genes in Ronan (29%). A portal protein, a major capsid protein, two tail assembly chaperones, a tail tape measure protein, holin, lysin A and lysin B, and immunity repressor were identified in both phages. A small and large terminase, major tail protein, excise, and integrase were identified in Jung but not in Ronan. In Ronan, we identified a single 3,024-bp-long terminase but no separate large or small terminase subunits. Ronan also contains a gene that spans the genome ends and 34 tRNA genes, both of which are common features of cluster C1 mycobacteriophages.The assembled genomes were annotated with DNA Master version 5.23.2., as described in references The GenBank and SRA accession numbers are listed in


Dengue fever is endemic and a leading health problem in Sri Lanka. Increased incidence of concurrent bacteremia in patients with dengue infection is a recognized complication. However, Staphylococcal endocarditis following dengue fever is uncommon. Quadricuspid aortic valve (QAV) is a rare congenital anomaly and few cases of infective endocarditis have been reported in QAV.A 32-year-old Sri Lankan male presented to the National Hospital of Sri Lanka with recurrence of fever and acute left hemiplegia following an uncomplicated recovery of dengue fever. He was diagnosed to have Staphylococcal infective endocarditis of quadricuspid aortic valve, with septic emboli to brain and spleen. He was managed with intravenous vancomycin initially, however, due to inadequate response, intravenous linezolid was added. He developed rhabdomyolysis with very high creatine phosphokinase leading to acute kidney injury, which settled with the cessation of linezolid. The patient succumbed to his illness despite aggressive antimicrobial therapy and maximum supportive care while being assessed for aortic valve replacement.This case illustrates three clinical issues that a clinician should be aware of. Firstly, the possibility of a serious secondary bacterial infection as a cause for recurrence of fever following dengue infection. Secondly, this case highlights the importance of identifying QAV as a cause for complicated infective endocarditis of increased severity. The report also denotes the value of being vigilant of linezolid induced rhabdomyolysis which had a causal relationship with the commencement of the drug and its cessation. Dengue fever is endemic and a leading health problem in Sri Lanka. A few case series have recognized an increased incidence of concurrent bacteremia in patients with dengue infection , 2.The quadricuspid aortic valve (QAV) is a rare congenital anomaly with an incidence of 0.008 to 0.043% [A 32-year-old Sri Lankan male presented to the National Hospital of Sri Lanka with acute left hemiplegia. Two weeks before the presentation, he was treated for uncomplicated dengue fever at a local hospital. The next day of discharge from the hospital, his fever recurred. On admission to our unit, he was febrile and confused. He had a dense paralysis of the left arm and leg with a GCS of 13/15 . His pulse rate was 120 bpm with a blood pressure of 130/60 mmHg and an early diastolic murmur in the lower left sternal edge compatible with aortic regurgitation (AR) was audible.3 (neutrophils 79%) haemoglobin-14.7 g/dL, platelets-101,000/mm3, C reactive protein-414 mg/l. A non-contrast computed tomography of head revealed multiple hypodensities in the right cerebral hemisphere with cerebral oedema.The investigations revealed the following: white cell count-19,840/mmStaphylococcus aureus (MRSA), which was sensitive to vancomycin and teicoplanin. Transoesophageal echocardiogram (TOE) showed two oscillating masses (6 × 4 mm and 12 × 6 mm) separately attached to the inferior side of the aortic valve with moderate AR  haemoglobin-11 g/dL, platelets-94,000/mm3, C reactive protein-394 mg/l. Therefore, on day six, the patient required mechanical ventilation and the addition of rifampicin and intravenous linezolid 600 mg twice daily. Before commencing linezolid, on day six, his serum creatinine was 0.98 mg/dl and creatine phosphokinase (CPK) was 142 U/l. On the fourth day of linezolid therapy, his fever started to settle, however, his GCS and inflammatory markers did not improve. On the same day, his CPK rose to 10,000 U/l with a serum creatinine of 1.1 mg/dl. On the seventh day of linezolid therapy, he developed acute rhabdomyolysis with raised CPK of 104,530 U/l and acute kidney injury (AKI) (serum creatinine- 3.9 mg/dl). Furthermore, the patient’s fever recurred and he became more haemodynamically unstable, requiring escalated inotropic support. As there were reported cases of linezolid induced rhabdomyolysis, we considered linezolid as the offending agent [Despite being on intravenous vancomycin for 4 days, his clinical status deteriorated as his consciousness further declined. The MRI brain which was done on day five revealed haemorrhagic transformation of ischaemic foci. On day six, his GCS was declining to 9/15 . He had a continuous fever and persistent sinus tachycardia of 120–130/min with the blood pressure of 110/70 mmHg maintained with 0.1 μg/kg/min intravenous noradrenaline infusion. The investigations done on the sixth day revealed no improvement: white cell count-24,000/mmThis patient’s recovery from dengue fever was complicated with MRSA endocarditis of aortic valve with septic embolization to the brain and spleen. He was found to have QAV. We could not find any reports of increased incidence of infective endocarditis in QAV. However, QAV endocarditis has increased risk for complications such as progressive AR, decompensated heart failure, and valve perforation .Hypotheses on the pathogenesis of concurrent bacteremia in patients with dengue include anti-NS1 antibody-induced endothelial cell apoptosis, which leads to endothelial dysfunction allowing bacteria to invade tissues . DefectiThere are two reported cases of linezolid induced rhabdomyolysis , 8. RhabThis case illustrates three clinical issues that a clinician should be aware of. Firstly, the possibility of a serious secondary bacterial infection as a cause for recurrence of fever following dengue infection. Secondly, this case highlights the importance of identifying QAV as a cause for complicated infective endocarditis of increased severity. The report also denotes the value of being vigilant of linezolid induced rhabdomyolysis which had a causal relationship with the commencement of the drug and its cessation.


P > 0.5). Celecoxib demonstrated the highest rate of Brooker class 0 (LOR 6.96), followed by diclofenac (LOR 6.94). Naproxen demonstrated the lowest rate of Brooker I HO (LOR 2.82), followed by celecoxib (LOR 3.52). Celecoxib demonstrated lowest rate of Brooker class II HO (LOR 1.66), class III (LOR), and class IV (LOR 0.25). The equation for global linearity detected no statistically significant inconsistency (P > 0.5) in all the comparisons. The present Bayesian network meta-analysis encourages the use of celecoxib as a prophylaxis for HO. These conclusions must be interpreted in light of the limitations of the present study. Future investigations are required to establish more definitely the role of celecoxib.Non-steroidal anti-inflammatory drugs (NSAID) have been recommended to prevent of heterotopic ossification (HO) after total hip arthroplasty (THA), but debates are still ongoing. The present Bayesian network meta-analysis of randomized clinical trials (RCTs) compared all available pathways of NSAID treatment as prophylaxis for HO after THA. The present Bayesian network meta-analysis was conducted according to The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions guidelines. All randomized clinical trials comparing two or more interventions to prevent HO after THA were considered for analysis. HO was classified according to Brooker. The quality of the methodological assessment was performed through the risk of bias summary tool of the Review Manager Software 5.3 . The network meta-analysis was performed through a STATA routine for Bayesian hierarchical random-effects model analysis, with log odd ratio (LOR) effect measure. Data from 26 studies  were collected. The mean follow-up was 10.50 ± 5.7 months. ANOVA showed good comparability among mean age and gender (Level of Evidence: I, Bayesian network analysis of RCTs. Heterotopic ossification (HO) is common after total hip arthroplasty (THA) , and is mentclasspt{minimaP (patients): total hip arthroplasty;I (intervention): prevention of HO;C (comparison): oral therapy drugs;O (outcomes): grade of HO;S (study type): randomized clinical trial (RCT).The present Bayesian network meta-analysis was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions guidelines . A primaTwo independent authors  performed the literature search in September 2020. First, the following databases were accessed: Pubmed, Embase, Scopus, Google Scholar. The search covered from initiation of the database to September 2020. The following keywords were used in combination: total hip arthroplasty, replacement, prosthesis, heterotopic ossification, NSAID, COX-inhibitors, impingement, indomethacin, naproxen, acetylsalicylic acid, celecoxib, meloxicam, rofecoxib, ibuprofen, diclofenac. Two independent authors  performed data extraction. If the title and abstract matched the topic, the full-text was accessed. The bibliographies of the considered articles were also screened for inclusion. Disagreements were debated and solved by a third author (MT).interventions used to prevent HO formation were considered for analysis in the present study. According to the authors’ language capabilities, articles in English, French, German, Italian, Portuguese and Spanish were considered. Only level I of evidence RCTs according to the Oxford Centre of Evidenced-Based Medicine [All randomized clinical trials comparing two or more Medicine  were incMedicine . Other cData extraction was performed by two independent authors . The following data were collected: generalities of the studies , duration of the follow-up (months), type of treatment and related protocol, number of samples, mean age and percentage of females among the study cohort. The outcome of interest was to evaluate the effect of oral non-steroidal anti-inflammatory drugs to prevent HO defined according to the modified Brooker Staging System Table . This clThe quality of the methodological assessment was performed through the risk of bias summary tool of the Review Manager Software 5.3 . For the present analysis, six items from each study were evaluated: allocation, randomization, blinding of the assessors, selective reporting, incomplete data, and unknown source of bias.P > 0.5 considered statistically significant. Analytical statistics was performed using the STATA Software/MP, Version 16 . The same software was used to produce an additional graphic  and percentile (PrI) intervals were set at 95%. Edge plots were performed in all comparisons to evaluate the amount of direct and indirect observations. Interval plots were produced in all comparisons to rank the treatments according to the reference value and related effect size. Funnel plots were generated to estimate the risk of publication bias by plotting the natural logarithm of an individual study effect size against the standard error of the natural logarithm of an individual study effect size. This methodology has been already used in previous studies [Higgins-I2 test was performed to evaluate heterogeneity. If the Higgins-I2 test was > 50%, high heterogeneity was detected, the data were analysed through a random model effect. If the Higgins-I2 test was < 50%, a fixed effect model was adopted. P values < 0.05 were considered statistically significant.The statistical analysis was performed by the first author (FM). For baseline comparability, the ANOVA test was performed using the IBM SPSS Software version 25, with a hic Fig.  that dis studies –21. A fuN = 27), a further 32 articles were excluded either because they did not report quantitative data (N = 9), language limitation (N = 3), animal or biomechanical or cadaveric studies (N = 12), focused only on radiation (N = 18), or delivered uncertain data (N = 2). Ultimately, 26 RCTs were included in the present study. The flow chart of the literature search is shown in Fig. The literature search resulted in 302 articles, of which 97 were RCTs. After removal of duplicates . Table Data from 6396  THAs were collected. The mean follow-up was 10.50 ± 5.7 months. The mean age of the patients was 66.30 ± 3.6 years. The mean duration of the drug administration for HO prevention was 20.95 ± 18.3 days. ANOVA showed good comparability in mean age and gender (P > 0.5) in all the comparisons. These results are shown in greater detail in Fig. Celecoxib demonstrated the highest rate of modified Brooker class 0 , followed by diclofenac . Naproxen demonstrated the lowest rate of HO according to the Brooker class II , followed by celecoxib . Celecoxib demonstrated the lowest rate of HO according to the Brooker class II , followed by acetylsalicylic acid . Celecoxib demonstrated the lowest rate of HO according to the Brooker class III , followed by naproxen . Celecoxib demonstrated the lowest rate of HO according to the Brooker class IV , followed by indomethacin . The equation for global linearity detected no statistically significant inconsistency (P = 0.6), class I , class II , class III , and class IV .Selective NSAIDs compared to the non-selective NSAIDs resulted not significant in all the comparisons: Brooker class 0  were not considered in the present study, representing another limitation. All the included articles, even those with follow-up shorter than 12 months, referred to the Brooker classification. We also must underline that, although HO formation generally is detectable early after surgery, its extent and Brooker grade can not be definitively assessed until 12 months after surgery. All the drugs were compared regardless to their daily intake or therapy duration. This represents an important limitation of the present study. As shown in Table In total hip arthroplasty, the use of celecoxib as prophylaxis was associated with the lowest rate of HO. Tenoxicam, acetylsalicylic acid, and meloxicam were associated with the highest rates of HO. Subgroup analysis of COX-2 non-selective versus selective COX-2 inhibitors NSAIDs showed no statistically consistent difference. These conclusions must be interpreted within the limitations of the present study. Further investigations are required to improve current evidences.


In adjusted models the odds of adequate protein intake were higher in participants with their own teeth or partial dentures (p = 0.036). Findings highlight the prevalence of low protein intake, uneven mealtime protein distribution and importance of dentition for adequate protein intake among adults in advanced age.Protein intake, food sources and distribution are important in preventing age-related loss of muscle mass and strength. The prevalence and determinants of low protein intake, food sources and mealtime distribution were examined in 214 Māori and 360 non-Māori of advanced age using two 24 h multiple pass recalls. The contribution of food groups to protein intake was assessed. Low protein intake was defined as ≤0.75 g/kg for women and ≤0.86 g/kg for men. A logistic regression model was built to explore predictors of low protein intake. A third of both women (30.9%) and men (33.3%) had a low protein intake. The main food group sources were beef/veal, fish/seafood, milk, bread though they differed by gender and ethnicity. For women and men respectively protein intake  was lowest at breakfast (10.1 and 13.0), followed by lunch (14.5 and 17.8) and dinner (23.3 and 34.2). Being a woman ( By 2051, the 85 years and over age group are expected to make up almost a quarter of the 65+ population .Those who are malnourished may have an inadequate protein intake which could contribute to possessing lower muscle mass and strength . Older aProtein can be obtained from both plant and animal sources; though they differ greatly in protein quality, rate of digestion and biological value, which affects the rate of skeletal muscle protein synthesis . For exaThe distribution of protein intake may also influence the maintenance of lean muscle mass. A key strategy for increasing the rate of protein synthesis is to evenly spread protein throughout the day, by aiming to have between 25 to 30 g of protein in each main meal . In the Therefore, the aim of this study was to investigate the intake, food sources, distribution, and adequacy of protein among Māori and non-Māori participants in Te Puāwaitanga o Ngā Tapuwae Kia Ora Tonu; Life and Living in Advanced Age: A Cohort Study in New Zealand.We conducted a cross-sectional study using data from the baseline and follow-up assessment of Life and Living in Advanced Age, A Cohort Study in New Zealand (LiLACS NZ), a longitudinal study of the very old in New Zealand . EligibiAt baseline in 2010, 671 participants completed a comprehensive questionnaire, conducted by trained interviewers and a health assessment by a trained nurse . ParticiA 12-month follow-up visit was undertaken in 2011 and included a physical assessment including weight, body mass index (BMI), fat mass and muscle mass as well as grip strength and level of physical activity. A detailed dietary assessment using the 24 h multiple pass recall (24 h MPR) on two separate days of the week was offered as part of that stage of the study.At baseline, we established whether the participants had practical help available. Participants responded either yes/no to: “When you need some extra help, can you count on anyone to help with daily tasks like grocery shopping, cooking, house cleaning, telephoning, give you a ride?” Current living arrangement was categorized as living alone (yes/no). The NZ Deprivation (NZDep) index obtained from the Ministry of Health was used as an indication of sociodemographic deprivation. The index was constructed from geo-coded addresses and included eight dimensions of material and social deprivation reflecting lack of income, employment, communication, transport, educational qualifications, home ownership and living space . During Health factors were established at baseline. Oral health was established by whether the participants wore dentures, had trouble with biting and chewing or had swallowing problems. Depression was assessed by the 15-item Geriatric Depression Screening Scale (GDS-15) , a relia2. Measurement of fat mass and muscle mass were estimated by bioimpedance using the Tanita scale . Grip strength was estimated using a Takei digital handgrip dynamometer-Grip D. The average value of three readings from the strongest hand was recorded [At follow-up the participants height was measured with a SECA 213 free-standing stadiometer two times unless the variance between both figures were greater than 1 cm then a third attempt was recorded . Weight recorded . A PhysiAs part of the follow-up assessment, 214 Māori and 360 non-Māori participants completed a 24 h MPR on two separate days of the week. The validity of the 24 h MPR is detailed elsewhere ,23. InteProtein intake was assessed using the NZ NRV’s  and estiAll foods from the 24 h MPR were allocated into one of thirty-three food items, used in the New Zealand Adult Nutrition Survey (NZANS) (2008/09) that contributed to protein intake . The topu test and independent t-test were used to determine differences between Māori and non-Māori, men and women for age, SF-12 physical health, SF-12 mental health, BMI, weight, grip strength, PASE score, fat mass percentage, muscle mass percentage, energy, protein (energy %), protein (g/day), protein (g/kg/day), protein distribution  and chi-square tests were used to test differences for categorical data , and low and adequate protein based on EAR). Protein from food groups were presented as a mean (±SD) and contribution to protein intake was expressed as a percentage (%) and adjusted for body weight (g/kg/day).The Kolmogorov-Smirnov and Shapiro-Wilk tests were used to check for normality for variables . Categorical data were presented as percentage with corresponding sample size. Normally distributed data were expressed as a mean and standard deviation (±SD); non-Gaussian distributed variables were expressed as medians and interquartile ranges (IQR). The Mann-Whitney p-value were removed in the model and p ≤ 0.2 was considered statistically significant enough to warrant inclusion. A logistic regression model was constructed to predict meeting the EAR for adequate protein intake (g/kg/day). The IBM SPSS Statistics 23 program was used to conduct the statistical analysis.A reduced multivariate regression model was built to predict protein intake in g/kg/day. Age, gender and ethnicity were included in the model and other potential predictors included practical support, depression, living alone, NZDep (score), wears dentures, chewing problems, swallowing difficulties, SF-12 physical and mental health scores, and pension only income. Variables with the highest The study was granted an ethics approval by the Northern Regional Ethics Committee of New Zealand in December 2009 (NTX/09/09/088).p < 0.001). More women  than men  lived alone (p < 0.001). Also, more women  had full mouth dentures compared to men  (p = 0.011). Rates of participation varied across the assessments both at baseline and at 12 months follow-up.At baseline 267 Māori and 414 non-Māori completed all measures. The sociodemographic health and physical characteristics of Māori and non-Māori men and women are illustrated in p < 0.001). Protein intake per day per kilogram of body weight was also significantly lower for women (58.6 g/day), (0.9 g/kg/day) compared to men (74.6 g/day), (1.0 g/kg/day) (p ≤ 0.001). Furthermore, women were more likely to consume less protein  than men; at breakfast , lunch  and dinner  (p < 0.001), respectively. Protein intake was greatest during the evening meal. On average women and men consumed 15.5% and 15.8% of their energy from protein, respectively (p = 0.003). Most participants met the EAR for protein intake for both women (69%) and men (67%). Māori  were more likely to meet the AMDR for protein than non-Māori  (p = 0.003).At 12 months follow up 224 Māori and 370 non-Māori completed all interview measures. There were 214 (96%) Māori and 360 (97%) non-Māori participants that completed the 2 × 24 h MPR dietary assessment and were weighed. As reported previously , % contrp = 0.003) and having depressive symptoms (p = 0.029) was associated with consuming less protein.Controlling for age and ethnicity, a reduced multivariate regression model was built to predict determinants of protein intake . For Māop = 0.036).Protein intake was not associated with health related QoL or socio-economic deprivation in either analysis.Overall, we found the median protein intakes were 0.9 g/kg/day for women and 1.0 g/kg/day for men. A third of participants , did not meet the EAR for older adults ≥70 years in Australia and New Zealand  .In Canada, among participants aged from 67 to 84 years in the NuAge study, the mean protein intake for men was 1.05 g/kg/day and 1.04 g/kg/day for women)  and amonThe optimal level of protein intake remains to be determined especially for those in advanced age. Australian and New Zealand recommendations for protein intake are aggregated for adults over 70 years and based on data derived from nitrogen balance studies in young adult men . The EARp = 0.003) and the presence of depressive symptoms (p = 0.029) predicted a lower protein intake adjusted for body weight. Conversely in the Newcastle 85+ study being a woman was associated with adequate protein intake (≥0.8 g/kg/day) in adjusted models [Using a reduced regression model adjusted for age and ethnicity we found being a woman  was observed in men compared to women (1.01 g/kg/day) . SimilarOur findings observed that the presence of depressive symptoms was associated with consuming less protein as had been observed among older men (>70 years) in South Korea; those with an inadequate protein intake were almost nine times more likely to be at risk of having depression . It has p = 0.036). Edentulism was more common in women (54%) than men (41%) which may partially account for the lower protein intake (g/kg/day) observed among women. In New Zealand removing all teeth at a young age was common practice during the early to mid-twentieth century and at this time New Zealand had the highest rate of edentulous people in a developed country [Using a logistic regression model controlled for age and ethnicity we found the oral health of the participants predicted meeting the EAR for protein for both women (≥0.75 g/kg/day) and men (≥0.86 g/kg/day). Participants with their own teeth or partial dentures were more likely to have an adequate protein intake than those with full dentures , with the highest intake at dinner and the least at breakfast. This may reflect the typical New Zealand eating pattern where protein is eaten mostly at the dinner meal. In the Newcastle 85+ study, 22% of the protein intake occurred in the morning, most (35%) during the “lunch” period followed by 21% over the “dinner” period . The latFor participants with an adequate protein intake (>EAR), beef/veal, bread and milk were the top three sources of protein and sources differed between sex and ethnic groups. In those with a low protein intake (≤EAR) bread was the main source followed by milk and beef/veal for Māori women and non-Māori men and women. This differed for Māori men where beef/veal was the main source followed by bread and fish and seafood. For Māori, fish and seafood (kāimoana) are traditional kai (foods) and hold a strong importance in Māori well-being  especialOur findings are consistent with the NZANS survey (2008/09) which observed the largest food contributors of protein were bread , followed by milk  and beef/veal  in both men and women aged over 70 years, respectively .Our study is the first to report the determinants of protein intake among Māori and non-Māori octogenarians in New Zealand using a repeat 24 h multiple pass recall which provides the best available method in this age group . Māori pThis study found a third of the participants did not meet the EAR for adequate protein intake. We observed an uneven mealtime protein distribution pattern, and the food group contributors to protein intake differed by gender and ethnicity. Depression was associated with protein intake, and the odds of consuming an adequate protein intake were higher in participants with their own teeth or partial dentures (adjusted models). Our findings highlight the prevalence and determinants of low protein intake among Māori and non-Māori of advanced age which may help to inform preventative interventions to improve the nutritional health of the oldest old.


This community-based study investigated the functional, physical and psychosocial impact of Temporomandibular Disorders (TMDs) in adolescents and young adults. It also determined the discriminative capacity of a TMDs-specific oral health related quality of life (OHRQoL) instrument and compared three formats of appraising OHRQoL data. Subjects were recruited from a local Polytechnic. The presence of TMDs was established with the Fonseca Anamnestic Index (FAI), whilst TMDs-specific OHRQoL was evaluated with the Oral Health Impact Profile–TMDs (OHIP-TMDs). Demographic information, FAI and OHIP-TMDs responses were gathered with an on-line questionnaire. Data was analysed using Mann-Whitney U-test, chi-square test and Spearman’s rho correlation with significance level set at 0.05.p  values < 0.001). For appraisal of extent and prevalence, significant differences were again observed  with the exception of the functional limitation and handicap domains.  Data from a total of 244 participants were compiled and examined. The “no TMDs” (NT) group consisted of 140 subjects  with a mean age of 20.41±3.29 years, while the “with TMDs” (WT) group composed of 104 subjects  aged 19.82±3.04 years. Significant differences in median severity scores were observed between subjects with and without TMDs for all OHIP-TMDs domains and total OHIP ( TMDs impacted physical and psychosocial well-being of adolescents and young adults. OHIP-TMDs, preferably appraised by severity, extent and prevalence, was able to discriminate between subjects with and without TMDs. It holds promise as a TMDs-specific OHRQoL instrument for epidemiological studies. Key words:Temporomandibular Disorders, Oral health, Quality of life, Biopsychosocial. Temporomandibular Disorders (TMDs) are a cluster of conditions that cause pain and dysfunction in the Temporomandibular joints (TMJs) and masticatory muscles. They are a significant public health problem affecting up to 11% of the general population with a higher female predominance , the preOHRQoL conveys a person’s assessment of his or her “well-being in connection with functional, psychological, and social aspects, as well as pain and discomfort when these are related to orofacial concerns”, . The intet al to address this lack  is the most popular . The 49-his lack . The OHIAlthough the OHIP-TMDs had been translated and validated in patients with TMDs ,15, its This community-based study was approved by the Polytechnic Institutional Review Board NYP/SHS2017/OHT/3). Subjects were recruited from 1st to 3rd year students from a local polytechnic. Based on a 95% confidence level, 5% margin of error for confidence interval, school student population of 2320 and an 11% prevalence of TMDs  , hardly ever (1 point), often (2 points), fairly often (3 points) and very often (4 points). OHIP-TMDs responses were subsequently assessed using the three formats proposed by Slade valence) . Domain Statistical analysis was performed with the Statistical Package for Social Sciences version 25  with significance level set at 0.05 for the total OHIP score and 0.01 for the domain scores. Normality of data was assessed using the Shapiro–Wilk test. As data was not normally distributed, Mann-Whitney U tests were used to explore the differences in the distribution of or median severity and extent scores between the NT and WT groups. Differences in prevalence were examined with the Chi-square or Chi-square exact tests. Correlations between severity and extent scores as well as prevalence rates were established using Spearman’s rho correlation (rs).p values < 0.001). Mean total OHIP severity score of the WT group was observed to be higher, 2.5 folds when compared to the NT group.The response rate was 15.8% (n=366) based on the total student population of 2320 and a third of surveys (n=122) were excluded due to incomplete entries. Data from a total 244 participants were compiled and examined accordingly. The NT group consisted of 140 subjects with a mean age of 20.41±3.29 years while the WT group composed of 104 subjects aged 19.82±3.04 years. Female to male ratios were 5.67:1 and 5.50:1 for the NT and WT groups respectively. The mean and median severity scores for both groups are reflected in p values < 0.05) with the exception of functional limitation and handicap. Median total OHIP extent scores were also significantly higher in the WT group . Mean total OHIP extent score was approximately 4 folds when compared to the NT group. FOVO prevalence rates are displayed in p values < 0.01).FOVO extent scores are shown in p values < 0.001). While correlations for the seven domains were largely perfect for extent-prevalence, they ranged from weak to moderate when severity scores and extent scores / prevalence were correlated. The highest correlation coefficient (rs) was observed for the psychological discomfort domain with rs = 0.67 and 0.66 for severity-extent and severity-prevalence respectively. For total OHIP, correlations were perfect for extent-prevalence (rs = 1.00) and moderate for severity-extent (rs = 0.62) and severity-prevalence (rs = 0.60).Correlations between severity scores, extent scores and prevalence rates are displayed in et al for East Asian adolescents and young adults (61%)  . The varet al contended that mean scores are “intrinsically meaningless” and that disparities in means “mask important and potentially different patterns in responses” between groups , anxiety or alcohol use disorders . MoreoveFor both FOVO extent and prevalence, TMDs was found to have no significant impact on the domains of functional limitation and handicap. Functional limitation is defined as the “loss of function of body parts or systems” while handicap is the “experience of disadvantage” . FunctioCorrelations between severity scores, extent scores and prevalence rates were all significant, but associations ranged from weak to perfect. As correlation coefficients between FOVO extent scores and FOVO prevalence rates was 0.99 to 1.00 for all domains and total OHIP, a mutual relationship existed between these two scoring formats. For reporting purposes, prevalence may be preferred over extent scores as it is simpler to understand and analyse. Correlations between severity scores and extent scores / prevalence were weak for all domains except psychological discomfort where relationships were moderately strong (rs = 0.66 to 0.67). Moderate correlations were also observed for total OHIP (rs = 0.60 to 0.62). Severity scores, which is the most popular format for reporting OHRQoL data, should thus be maintained as a key descriptive reporting standard. Total OHIP-TMDs severity scores were reported to be 7.38 ± 10.10 and 33.40 ± 17.07 for a cohort of control and TMDs patients respectively . In the et al (The present study and OHIP-TMDs have certain constraints. The study involved a convenience sample with participants recruited from only a single polytechnic. The results may possibly be gender-biased as subjects were predominantly females who are more susceptible to TMDs, pain-related disability and psychological distress . The higet al . The OHIet al .TMDs impacted physical and psychosocial well-being of adolescents and young adults. OHIP-TMDs was able to discriminate between subjects with and without TMDs, and is a promising TMDs-specific OHRQoL measure for epidemiological studies. As the three formats of appraising OHRQoL data yielded dissimilar results, the use of extent and / or prevalence in addition to severity scores is advocated for future OHRQoL work. Further validation of the OHIP-TMDs should be performed using item response theory models.