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The objective was to elucidate the effects of dietary supplementation with guanidinoacetic acid (GAA) on performance, egg quality and the liver antioxidant activity of laying hens. A total of 128, 72-week-old ISA Brown laying hens were randomly divided into four equal groups (32 birds), and each subgroup had eight replicates (four birds/cage). The control group (GAA0) fed the basal diet with no supplements, while the other experimental groups fed the basal diets supplemented with 0.5 (GAA1), 1.0 (GAA2) and 1.5 (GAA3) g of GAA/kg diet. The experiment lasted for 6 weeks. The addition of GAA at a rate of 1.5 g kg−1 significantly increased the hen-day egg production and egg mass as compared to the control group (P = 0.016 and 0.003, respectively). Although the egg weight was not affected (P = 0.521) by the dietary supplements, the shell ratio, shell thickness, yolk index and Haugh units increased linearly with the increase in the dietary supplements of the GAA (P = 0.036, 0.001, 0.012 and 0.004, respectively). The liver MDA levels decreased linearly with the increment in the dietary levels of the GAA (P = 0.012). Birds in the GAA2 and GAA3 showed a significantly higher liver nitric oxide level (52.50 and 54.21 mg/g, respectively) when compared with GAA0 and GAA1 groups (P = 0.029). Compared to the GAA0 group, all GAA-supplemented groups showed significantly higher liver ATP levels (P = 0.047). In conclusion, the dietary GA supplements at doses of 1.0 or 1.5 g kg−1 may improve the laying performance, antioxidant activity and the status of cellular energy metabolism in laying hens.
Recently, oral vancomycin prophylaxis (OVP) has been suggested for the prevention of Clostridium difficile infection (CDI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of this approach.
Systematic review and meta-analysis.
We conducted a computerized search of MEDLINE, EMBASE, and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for eligibility. Relevant data were extracted and analyzed. Publication bias was assessed using the Egger test.
Ultimately, 8 retrospective studies and 1 prospective study examining 2174 patients, published between 2016 and 2019 were included in the review. OVP was associated with decreased CDI (odds ratio, 0.263; 95% confidence interval, 0.13–0.52) with considerable heterogeneity (I2 = 61%). Meta-regression showed that total daily dose of OVP correlated with CDI, explaining 100% of heterogeneity between studies. Furthermore, 3 studies evaluated the risk of vancomycin-resistant enterococci (VRE) infection after OVP and found no significant increase.
Our results suggest that OVP might decrease CDI rates in at-risk populations, although this conclusion should be interpreted with caution. Higher daily doses of OVP might increase CDI. Although the use of OVP in high-risk patients may reduce CDI, this suggestion has yet to be validated by prospective blinded randomized controlled trials.
Schistosomiasis is a multifactorial disease that includes environmental, behavioral, parasitic, vector, and host factors. This study aimed to assess the protective effect of single and polyvalent antigens from cercarial antigen preparations (CAPs), soluble worm antigen preparations (SWAPs), and soluble egg antigens (SEAs) which were used as candidate vaccines in an experimental model of Schistosoma mansoni-infected mice. The efficiency of the antigens was tested by determining their effects on fecal egg count, egg viability analysis, and tissue egg counts. Histological and morphometric analyses of granulomas in liver and intestine tissues were performed. In the present study, all immunized groups showed a significant reduction in the average fecal egg count and tissue egg load compared with infected mice. The most substantial reduction in fecal egg count was observed in the combined vaccinated group (23.23 ± 3.2). The group vaccinated with CAP before infection showed the highest reduction in tissue egg load (liver and intestine: 85.22 and 91.70%, respectively). Immunized animals showed a highly significant reduction in the numbers of hepatic granulomas compared with the infected non-immunized group. In conclusion, combining these different antigens (CAP, SWAP, and SEA) augments the protective immunity compared with other immunized groups.
An inspired metamaterial-based highly efficient monopole antenna displaying wide-/dual-band resonances along with self-filtering properties is presented. The monopole has high out-of-band suppression characteristics that lead to very close to 0 dB band-stop between the antenna dual resonant bands. The antenna operates at the two WLAN services of 2.65–3.25 and 5–7 GHz with stopband with total reflection at 4.5 GHz. The designed filtering characteristics are based on current coupling for the dual-band functions and current neutralization for the stopband function. Moreover, the proposed antenna has a very high radiation efficiency of 97 and 99% at 3 and 6 GHz, respectively. Furthermore, the proposed antenna exhibits an omni-directional radiation pattern with coplanar waveguide feed for simple integration with passive/active devices. Moreover, the antenna properties are achieved with a compact antenna size (30 × 30 mm2). With all presented results, the proposed antenna is very competitive over recent relevant antennas. In addition, a very good agreement between theoretical, full-wave simulations and measurements is achieved.
A compact monopole antenna backed with a 1 × 2 textile-based artificial magnetic conductor (AMC) array is proposed. Textile was mainly selected for the AMC materials according to an investigation that took place between different AMC substrate materials, where it was settled that the textile one displayed the highest antenna gain and efficiency. The monopole antenna and the AMC, distanced apart by 5 mm, combined form the integrated design. It operates at 2.4 GHz, which was particularly selected as the resonant frequency for wirelessly sending the subject's symptoms data via Wi-Fi, with realized gain and total efficiency of 6.76 dBi and 88.4%, respectively, in free space. Separated by 3 mm from the specific anthropomorphic mannequin human hand model, it displays a realized gain and total efficiency of 4.06 dBi and 44.39%, respectively, in a flat condition. Furthermore, it exhibits a specific absorption rate (SAR) of 1.8 W/kg averaged over 10 g of tissue. When bent over the human hand model, it performs well and exhibits a maximum SAR of 0.521 and 0.406 W/kg, averaged over 1 and 10 g of tissues, respectively. As a result of such outcomes, the proposed integrated design can be nominated for wearable hand/wrist and Wi-Fi applications.
This study aims to assess the perception and attitude of Emergency medical services (EMS) providers toward working during disease outbreaks, and the factors that may influence their decisions to ultimately work or not.
This is a cross-sectional study assessing the attitude of EMS providers to work during disease outbreaks. Descriptive statistics and regression analyses were performed to assess attitudes towards reporting for duty and factors that influence providers’ decisions.
Of the 500 surveys distributed, 466 (93.2%) were complete and included for analysis. The majority of participants (70.2%) are male with a mean age of 27 (SD 4.3) years. The study found that the majority (71.1%) of participants are willing to come to work during disease outbreaks. The study found seven predictors of reporting for duty. Confidence that employer will provide adequate protective gear was the most significant predictor (OR 3.95; 95% CI = 2.31-5.42). Concern for family safety was the most important barrier against coming to work (OR 0.40; 95% CI =0.21-0.73).
Providing adequate supplies of protective gear along with knowledge and training for disease outbreak are the main factors that enhance providers to fulfill their work expectations.
To predict skull base osteomyelitis in patients with necrotising otitis externa using diffusion-weighted imaging.
A retrospective analysis was conducted of 25 necrotising otitis externa patients with skull base osteomyelitis (n = 10) or without skull base involvement (n = 14) who underwent a single-shot diffusion-weighted imaging of the skull base.
The respective mean apparent diffusion coefficient values of the skull base, as determined by two reviewers, were 0.851 ± 0.15 and 0.841 ± 0.14 ×10-3mm2/s for the skull base osteomyelitis patients, and 1.065 ± 0.19 and 1.045 ± 0.20 ×10-3mm2/s for the necrotising otitis externa patients without skull base involvement. The difference in apparent diffusion coefficients between the groups was significant, for both reviewers (p = 0.008 and 0.012). The optimal threshold apparent diffusion coefficient for predicting skull base osteomyelitis in necrotising otitis externa patients was 0.945 ×10-3mm2/s and 0.915 ×10-3mm2/s, with an area under the curve of 0.825 and 0.800, accuracy of 87.5 and 83.3 per cent, sensitivity of 85.7 and 90.0 per cent, and specificity of 90.0 and 78.6 per cent, for each reviewer respectively.
Apparent diffusion coefficient is a non-invasive imaging parameter useful for predicting skull base osteomyelitis in necrotising otitis externa patients.
Although refugees are at an increased risk to suffer from mental disorders, as compared to other immigrants, little is known about possible differences in treatment response and service utilization.
The current study includes data from two separate samples of Iraqi refugees and Arab immigrants. Prevalence of physician-diagnosed mental disorders along with treatment response and utilization data was collected from medical records or by surveys. Data was collected from 307 refugees and 326 immigrant controls.
The prevalence of depression was significantly greater in refugees as compared to immigrants (54% vs. 26%; p< .001). There were no differences between groups in diagnosed anxiety disorders. In addition, self reported complaints of depression (33% vs. 3.1%; p< .001), anxiety (20% vs. 4%; p< .001), and sleep difficulties (15% vs. 2%; p< .001) were more prevalent among refugees than immigrants. In general, treatment response was poor for both groups; however, for longer term patients, treatment response was significantly better (44% recovery vs. 15% recovery; p< .001) for immigrants than refugees. Typical common psychosomatic symptoms were more prevalent and associated with increased health care utilization in refugees as compared to immigrants.
Results suggest that treatment offered to refugees is far from effective. There is a need to review health systems factors in order to promote cost-effective and timely mental health services for refugees, not least with the current influx of Iraqi refugees commonly suffering from mental and adjustment disorders.
This study investigated the point prevalence of extrapyramidal movement disorders in patients with chronic schizophrenia and related disorders who are currently treated by Northland District Health Board (DHB) mental health services, New Zealand. The study also investigated evidence of variation in the point prevalence of these disorders based on the ethnicity of the patients (indigenous Māori patients and non-Māori).
151 patients, who had received antipsychotic medication for 3 months or more, were recruited as participants for the study using randomised computer software. Ethnicity was documented using self-identification. Akathisia was assessed using the Barnes Akathisia Rating Scale (BARS). The Abnormal Involuntary Movement Scale (AIMS) was used to assess tardive dyskinesia and extrapyramidal side effects (EPSE) were assessed by the Simpson-Angus Rating Scale (SAS).
9.3 % had akathisia using Barnes scale, 43% had Parkinsonian symptoms on SAS scale, and 18.5 % had tardive dyskinesia using AIMS scale. The analysis failed to show any statistically significant differences based on ethnicity (indigenous Māori and non-Māori). P = 0.284, 0.176, and 0.201 for Barnes, SAS and Aims respectively.
The findings suggest that the prevalence of neuroleptics-induced movement disorders in psychotic patients within Northland DHB (9%-43%), is similar to the documented international figures. These findings also indicate that there is no significant difference based on ethnicity between Māori and non-Māori in terms of movement disorders profile.
A review of studies examining the frequency of depression in schizophrenia found prevalence rates ranging from 7% to 75%. This wide range could be reasoned by the in proper selection of the instruments used for assessment.
To answer a question; is there a relation between the used depression scale and the category of schizophrenia and/or depression.
To compare Hamilton (HAMD) and Calgary (CDRS) depression scales in assessing depression in schizophrenia.
385 schizophrenic patients were recruited from Institute of Psychiatry Ain Shams University hospitals and asked to complete Structured Clinical Interview for Diagnosis section for schizophrenia and depression, socio-demographic sheet, medical history sheet, HAMD, CDRS, and Positive and negative Psychotic Symptoms Scale (PANSS).
Depression was found as; disorder (66.2% by HAMD and 39.2% by CDRS), no depression (18.2% by HAMD and 33.2% by CDRS) and symptoms (15.6% by HAMD and 27.5% by CDRS). Agreement of both scales in diagnosing depressive disorder is higher in chronic schizophrenia (62%) than in acute one (50%) and found mostly in continuous and remittent course. No significant correlation was found between CDRS and PANSS scores, while for HAMD, total score for depression was significantly correlated with all psychotic symptoms scores only in schizophrenic patients with depressive disorder.
CDRS is more valid in classification of depression categories in schizophrenia than HAMD. It is more sensitive and specific instrument for assessing depression in schizophrenia than HAMD. However, HAMD may be suitable with acute schizophrenia and remittent course.
Asian Houbara Chlamydotis macqueenii is a vulnerable flagship species specific to steppe, desert and semi-desert habitats of the Middle East and Central Asia. Iran provides a critical corridor in the middle of Asian Houbara’s migratory route and also hosts a relatively large proportion of wintering and breeding populations. The aim of this study was to assess the distribution and habitat suitability of both wintering and breeding populations of Asian Houbara in Iran and evaluate the effectiveness of the existing protected area network for long-term protection of the species. For this purpose, 644 occurrence points for wintering and 216 points for breeding birds were collected from 17 Iranian provinces during 2015 to 2017. We then used a consensus species distribution modelling (SDM) approach using 11 uncorrelated environmental variables to explore the distribution of Asian Houbara habitats. Results showed that climatic and topographic variations have the most significant influence on the regional-scale distribution of Asian Houbara. Of the suitable habitats recognised for the wintering and breeding populations, 40.6% and 29.6% respectively overlapped with the extent of the protected network. A high level of spatial niche similarity (78%) was observed between wintering and breeding populations. The central, eastern and south-central Iranian semi-arid regions and desert landscapes hosted the majority of both wintering and breeding houbara occurrences. Results of this study could be used for adopting direct management planning and raising the protection level of important no-hunting areas.
This study aimed to: (i) characterize cultured granulosa cells (GCs) from different follicle sizes morphologically and molecularly; and (ii) select a suitable model according to follicular size that maintained GC function during culture. Buffalo ovaries were collected from a slaughterhouse and follicles were classified morphologically into: first group ≤ 4 mm, second group 5–8 mm, third group 9–15 mm and fourth group 16–20 mm diameter. GC pellets were divided into two portions. The first portion served as the control fresh pellet, and the secondwas used for 1 week for GC culture. Total RNA was isolated, and qRT-PCR was performed to test for follicle-stimulating hormone receptor (FSHR), cytochrome P450 19 (CYP19), luteinizing hormone/choriogonadotropin receptor (LHCGR), proliferating cell nuclear antigen (PCNA), apoptosis-related cysteine peptidase (CASP3), anti-Müllerian hormone (AMH), and phospholipase A2 group III (PLA2G3) mRNAs. Estradiol (E2) and progesterone (P4) levels in the culture supernatant and in follicular fluids were measured using enzyme-linked immunosorbent assay (ELISA). Basic DMEM-F12 medium maintained the morphological appearance of cultured GCs. The relative abundance of FSHR, CYP19, and LHCGR mRNAs was 0.001 ≤ P ≤ 0.01 and decreased at the end of culture compared with the fresh pellet. There was a fine balance between expression patterns of the proliferation marker gene (PCNA) and the proapoptotic marker gene (CASP3). AMH mRNA was significantly increased (P < 0.001) in cultured GCs from small follicles, while cultured GCs from other three categories (5–8 mm, 9–15 mm and 16–20 mm) showed a clear reduction (P < 0.001). Interestingly, the relative abundance of PLA2G3 mRNA was significantly (P < 0.001) increased in all cultured GCs. E2 and P4 concentrations were significantly (P < 0.001) decreased in all cultured groups. Primary cultured GCs from small follicles could be a good model for better understanding follicular development in Egyptian buffaloes.
We introduce a model for the spreading of fake news in a community of size n. There are
$j_n = \alpha n - g_n$
active gullible persons who are willing to believe and spread the fake news, the rest do not react to it. We address the question ‘How long does it take for
$r = \rho n - h_n$
persons to become spreaders?’ (The perturbation functions
are o(n), and
$0\le \rho \le \alpha\le 1$
.) The setup has a straightforward representation as a convolution of geometric random variables with quadratic probabilities. However, asymptotic distributions require delicate analysis that gives a somewhat surprising outcome. Normalized appropriately, the waiting time has three main phases: (a) away from the depletion of active gullible persons, when
$0< \rho < \alpha$
, the normalized variable converges in distribution to a Gumbel random variable; (b) near depletion, when
$0< \rho = \alpha$
$h_n - g_n \to \infty$
, the normalized variable also converges in distribution to a Gumbel random variable, but the centering function gains weight with increasing perturbations; (c) at almost complete depletion, when
$r = j -c$
, for integer
, the normalized variable converges in distribution to a convolution of two independent generalized Gumbel random variables. The influence of various perturbation functions endows the three main phases with an infinite number of phase transitions at the seam lines.
In this study, the radiation contamination dose (RCD) for different combinations of electron energy/distance, applicator and radius around the light intraoperative accelerator (LIAC), a high dose per pulse dedicated intraoperative electron radiotherapy machine, has been estimated. Being aware about the amount of RCDs is highly recommended for linear medical electron accelerators.
Methods and methods:
Monte Carlo Nuclear Particles (MCNP) code was used to simulate the LIAC® head and calculate RCDs. Experimental RCDs measurements were also done by Advanced Markus chamber inside a MP3-XS water phantom. Relative differences of simulations and measurements were calculated.
RCD reduction by distance from the machine follows the inverse-square law, as expected. The RCD was decreased by increasing angle from applicator walls opposed to the electron beam direction. The maximum differences between the simulation and measurement results were lower than 3%.
The RCD is strongly dependent on electron beam energy, applicator size and distance from the accelerator head. Agreement between the MCNP results and ionometric dosimetry confirms the applicability of this simulation code in modelling the intraoperative electron beam and obtaining the dosimetric parameters. The RCD is a parameter that would restrict working with LIAC in an unshielded operative room.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Plant-derived additives are used to maintain the health and growth performance of livestock. The use of red pepper oil (RPO) has recently attracted considerable scientific interest mainly due to its potential benefits for animals and humans. The present study was conducted to evaluate the effect of dietary supplementation with RPO on growth performance, carcass measurements, antioxidant status and immunity of growing quails between 1 and 5 weeks of age. A total of 240 growing quails (1-week old) were distributed into 5 equal groups consisting of 48 birds (4 replicates of 12 birds each). The first group was fed a basal diet without RPO (0 g/kg diet), and the second, third, fourth and fifth groups received diets containing RPO (0.4, 0.8, 1.2, 1.6 g/kg diet, respectively). The experiment lasted for 5 weeks. At age of 5 weeks, quails were slaughtered for carcass examinations, microbiological analysis of intestine and to determine blood constituents. Data were statistically analyzed by one-way ANOVA. Quails fed with 0.8 g RPO/kg diet showed 12.14%, 14.4% and 15% improvement in live BW, body weight gain and feed conversion ratio, respectively, compared with the control group. Quails that received diets with 1.2 g RPO consumed more feed than the others during the total period (1 to 5 weeks). Plasma globulin levels were significantly decreased (P = 0.0102), but albumin/globulin ratio was significantly increased (P = 0.0009) in birds fed diets containing RPO (0.4 and 1.2 g/kg) compared with those in the control group. Activity of liver enzymes in the plasma was nonsignificantly decreased in quails supplemented with 0.8 g RPO/kg diet compared with those in the control group. Activities of antioxidant enzymes (glutathione and catalase) in the group fed on diets supplemented with RPO (0.8 g/kg) were significantly higher than those in the control group. The inclusion of RPO (0.8 g/kg diet) in quail diets improved (P < 0.05) plasma lipid profile and also decreased pH of the caecal content (P = 0.0280) compared with those in the control group. The caecal bacterial population, Salmonella spp., coliform and Escherichia coli, were lowered (P < 0.05) in the groups treated with RPO (0.8, 1.2 and 1.6 g/kg) compared with those in the control group. In conclusion, dietary supplementation of RPO (0.8 g/kg) can enhance the performance and antioxidant indices and decrease intestinal pathogens and thus improve the health status of Japanese quail.
The convex hull of a sample is used to approximate the support of the underlying distribution. This approximation has many practical implications in real life. To approximate the distribution of the functionals of convex hulls, asymptotic theory plays a crucial role. Unfortunately most of the asymptotic results are computationally intractable. To address this computational intractability, we consider consistent bootstrapping schemes for certain cases. Let
be a sequence of independent and identically distributed random points uniformly distributed on an unknown convex set in
). We suggest a bootstrapping scheme that relies on resampling uniformly from the convex hull of
. Moreover, the resampling asymptotic consistency of certain functionals of convex hulls is derived under this bootstrapping scheme. In particular, we apply our bootstrapping technique to the Hausdorff distance between the actual convex set and its estimator. For
, we investigate the asymptotic consistency of the suggested bootstrapping scheme for the area of the symmetric difference and the perimeter difference between the actual convex set and its estimate. In all cases the consistency allows us to rely on the suggested resampling scheme to study the actual distributions, which are not computationally tractable.
Optical stylets are airway tools, which combine features of fiberoptic bronchoscopes and intubation stylets. These devices use fibers to transmit the image to an eyepiece or camera, which can be attached to the eyepiece for viewing on a monitor. Optical stylets are designed to be used independently, with laryngoscopes, or with SGA devices. There are wide variations in optical stylet length, malleability, and light sources. The common feature of these devises is their light source, which enables the stylet to be used as a lightwand, while the fiberoptic capability enables visualization of the laryngeal inlet.
The present study aimed to evaluate the quality of fresh sushi in Egypt. Fifty samples of sushi (Salmo salar) were collected from restaurants in Alexandria, Egypt. Paraffin, semi-thin and ultra-thin sections were used for parasitological analysis by light and transmission electron microscopy. Bacteria were isolated by the dilution plate and direct plate methods and identified by a Vitek system. Twenty (40%) of the total examined samples showed microsporidia and helminth metacercariae infections. Histochemical stains showed distinct pinkish-red pyriform microspores embedded in muscular tissue stained with Gram, periodic acid-Schiff (PAS), and Ziehl–Neelsen (ZN) stains. Semi-thin sections showed double membrane xenoma-inducing granulomas containing spores at different developmental stages. Empty sporophorous vesicles and free spores were observed in the electron microscopic images. A bacteriological assay showed forty samples (80%) contaminated with human pathogenic bacteria with the average total bacterial counts ranging from 32 to 526 CFU/g. Four species of human pathogenic bacteria were identified in the examined samples, namely Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Serratia plymuthica in 40, 38, 11, and 6 samples, respectively. These constitute the first record of fresh sushi product in Egypt and indicate the potential pathogenicity associated with raw seafood products.
CD34, vimentin, and vascular endothelial growth factor immunohistochemical analysis and electron microscopic tools were employed to record the initial appearance of telocytes (TCs) and stage-by-stage variations in TC localizations in the developing rabbit lung. TCs could not be identified in the primitive embryonic lung until day 18 of gestation. In the pseudoglandular lung, CD34+ TCs had been recorded under the cartilage of the main bronchus, in the wall of large-sized pulmonary vessels and large epithelial tubes. In the canalicular phase, TCs could be demonstrated in the smooth muscle layer of the bronchioles including the terminal ones. The strength of CD34 immunoreactive signals had been amplified by age until the day of parturition. Ultrastructurally, TCs consisted of a tiny body and exceptionally long telopodes (Tps). The Tp consisted of alternating thin segments (podomers) and dilated ones (podoms). The Tp sometimes branched with a dichotomous pattern. TCs interconnected in a network either by homocellular junctions with neighboring TCs or by heterocellular junctions with smooth muscle cells and alveolar cells. Collectively, early detection of TCs in pulmonary vessels suggests a potential role for TCs in their angiogenesis. For the lung tissue, TCs seem to be involved in the regulation of lung histogenesis.