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Cadmium and lead contents were determined in pork and duck liver pastes produced in Spain. The average concentration levels that were measured were 19 ng/g for cadmium and 578 ng/g for lead in pork liver pastes and 14 ng/g for cadmium and 15 7 ng/g for lead in duck liver pastes. The possible sources of these trace elements were investigated: product formulation, technological process and packaging. It has beenobserved that the contents of lead in pork liver pastes are higher than would be expected from the liver content alone, and that the mainsource of lead is the tin container. [ABSTRACT FROM AUTHOR]

The contents of four essential elements, Mn, Fe, Cu, Zn, were determined in 152 samples of pork and duck liver paste produced in Spain. The average concentration levels that were measured are 1.2 mu g/g forMn, 51.6 mu g/g for Fe, 6.1 mu g/g for Cu and 22.2 mu g/g for Zn in pork liver pastes and 0.8 mu g/g for Mn, 32.3 mu g/g for Fe, 2.7 mu g/g for Cu and 12.9 mu g/g for Zn in duck liver pastes. The possible sources of these trace elements were investigated: product formulation, technological processing and packaging. Liver, the basic raw material, is the main source of trace elements in the final product; significantly high concentrations have been observed for all of the elements that were analysed in the pork liver pastes compared with the duck liver pastes. [ABSTRACT FROM AUTHOR]

Current diagnostic methods for prion diseases only work in late stages of the disease when neurodegeneration is irreversible. Therefore, biomarkers that can detect the disease before the onset of clinical symptoms are necessary. High-throughput discovery proteomics is of great interest in the search for such molecules. Here we used mass spectrometry to analyse the cerebrospinal fluid proteome in an animal prion disease: preclinical and clinical sheep affected with natural scrapie, and healthy sheep. Interestingly, we found 46 proteins in the preclinical stage that were significantly altered ( p  < 0.01) compared to healthy sheep, mainly associated with biological processes such as stress and inflammatory responses. Five of them were selected for validation by enzyme-like immunosorbent assay: synaptotagmin binding, cytoplasmic RNA interacting protein (SYNCRIP), involved in nucleic acid metabolism; phospholipase D3 (PLD3) and cathepsin D (CTSD), both related to lysosomal apoptosis; complement component 4 (C4), an element of the classical immune response; and osteopontin (SPP1), a proinflammatory cytokine. These proteins significantly increased in the preclinical stage and maintained their levels in the clinical phase, except for CTSD, whose concentration returned to basal levels in the clinical group. Further research is ongoing to explore their potential as preclinical biomarkers of prion diseases.

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities. Whereas oral and intraperitoneal transmissions produced identical neuropathological outcomes in GtE and GtQ mice and preserved the naturally convergent conformations of elk and deer CWD prions, intracerebral transmissions generated CNS prion strains with divergent biochemical properties in GtE and GtQ mice that were changed compared to their native counterparts. While CWD replication kinetics remained constant during iterative peripheral transmissions and brain titers reflected those found in native hosts, serial intracerebral transmissions produced 10-fold higher prion titers and accelerated incubation times. Our demonstration that peripherally and intracerebrally challenged Gt mice develop dissimilar CNS diseases which result from the propagation of distinct CWD prion strains points to the involvement of tissue-specific cofactors during strain selection in different host compartments. Since peripheral transmissions preserved the natural features of elk and deer prions, whereas intracerebral propagation produced divergent strains, our findings illustrate the importance of experimental characterizations using hosts that not only abrogate species barriers but also accurately recapitulate natural transmission routes of native strains., Competing Interests: Competing interests statement:The authors declare no competing interest.

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrP Sc immunohistochemistry staining in the brainstem and the absence of detectable PrP Sc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain., (© 2024. The Author(s).)

Prions or prion-like aggregates such as those composed of PrP, α-synuclein, and tau are key features of proteinopathies such as prion, Parkinson's and Alzheimer's diseases, respectively. Their presence on solid surfaces may be biohazardous under some circumstances. PrP prions bound to solids are detectable by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays if the solids can be immersed in assay wells or the prions transferred to pads. Here we show that prion-like seeds can remain detectable on steel wires for at least a year, or even after enzymatic cleaning and sterilization. We also show that contamination of larger objects with pathological seeds of α-synuclein, tau, and PrP can be detected by simply assaying a sampling medium that has been transiently applied to the surface. Human α-synuclein seeds in dementia with Lewy bodies brain tissue were detected by α-synuclein RT-QuIC after drying of tissue dilutions with concentrations as low as 10-6 onto stainless steel. Tau RT-QuIC detected tau seeding activity on steel exposed to Alzheimer's disease brain tissue diluted as much as a billion fold. Prion RT-QuIC assays detected seeding activity on plates exposed to brain dilutions as extreme as 10-5-10-8 from prion-affected humans, sheep, cattle and cervids. Sampling medium collected from surgical instruments used in necropsies of sporadic Creutzfeldt-Jakob disease-infected transgenic mice was positive down to 10-6 dilution. Sensitivity for prion detection was not sacrificed by omitting the recombinant PrP substrate from the sampling medium during its application to a surface and subsequent storage as long as the substrate was added prior to performing the assay reaction. Our findings demonstrate practical prototypic surface RT-QuIC protocols for the highly sensitive detection of pathologic seeds of α-synuclein, tau, and PrP on solid objects., Competing Interests: BC, CDO, BG and AH are inventors on patent applications pertaining to RT-QuIC technology. The other authors have declared that no competing interests exist. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Government., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Scrapie, a naturally occurring prion disease affecting goats and sheep, comprises classical and atypical forms, with classical scrapie being the archetype of transmissible spongiform encephalopathies. This review explores the challenges of scrapie diagnosis and the utility of various biomarkers and their potential implications for human prion diseases. Understanding these biomarkers in the context of scrapie may enable earlier prion disease diagnosis in humans, which is crucial for effective intervention. Research on scrapie biomarkers bridges the gap between veterinary and human medicine, offering hope for the early detection and improved management of prion diseases.

The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrP Sc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle., (© 2023. L’Institut National de Recherche en Agriculture, Alimentation et Environnement (INRAE).)

The role of the glycosylation status of PrPC in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrPC. Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrPC-expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrPC is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties., Competing Interests: The authors have declared that no competing interests exist.

The non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrP C ) into an abnormal and misfolded isoform known as PrP Sc . These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease or Alzheimer's disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrP C , were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models., (© 2021. The Author(s).)

Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different. In this study, we characterized the prion strains responsible for hGH-iCJD cases originating from UK (n = 11) and France (n = 11) using human PrP expressing mouse models. The cases included PRNP MM, MV and VV genotypes from both countries. UK and French sporadic CJD (sCJD) cases were included as controls. The prion strains identified following inoculation with hGH-iCJD homogenates corresponded to the two most frequently observed sCJD prion strains (M1 CJD and V2 CJD ). However, in clear contradiction to the initial hypothesis, the prion strains that were identified in the UK and the French hGH-iCJD cases were not radically different. In the vast majority of the cases originating from both countries, the V2 CJD strain or a mixture of M1 CJD  + V2 CJD strains were identified. These data strongly support the contention that the differences in the epidemiological and genetic profiles observed in the UK and France hGH-iCJD cohorts cannot be attributed only to the transmission of different prion strains., (© 2021. The Author(s).)

Neurotrophins constitute a group of growth factor that exerts important functions in the nervous system of vertebrates. They act through two classes of transmembrane receptors: tyrosine-kinase receptors and the p75 neurotrophin receptor (p75 NTR ). The activation of p75 NTR can favor cell survival or apoptosis depending on diverse factors. Several studies evidenced a link between p75 NTR and the pathogenesis of prion diseases. In this study, we investigated the distribution of several neurotrophins and their receptors, including p75 NTR , in the brain of naturally scrapie-affected sheep and experimentally infected ovinized transgenic mice and its correlation with other markers of prion disease. No evident changes in infected mice or sheep were observed regarding neurotrophins and their receptors except for the immunohistochemistry against p75 NTR . Infected mice showed higher abundance of p75 NTR immunostained cells than their non-infected counterparts. The astrocytic labeling correlated with other neuropathological alterations of prion disease. Confocal microscopy demonstrated the co-localization of p75 NTR and the astrocytic marker GFAP, suggesting an involvement of astrocytes in p75 NTR -mediated neurodegeneration. In contrast, p75 NTR staining in sheep lacked astrocytic labeling. However, digital image analyses revealed increased labeling intensities in preclinical sheep compared with non-infected and terminal sheep in several brain nuclei. This suggests that this receptor is overexpressed in early stages of prion-related neurodegeneration in sheep. Our results confirm a role of p75 NTR in the pathogenesis of classical ovine scrapie in both the natural host and in an experimental transgenic mouse model.

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.

Transmissible spongiform encephalopathies (TSEs) are a group of invariably fatal neurodegenerative disorders. The causal agent is an aberrantly folded isoform (PrP Sc or prion) of the endogenous prion protein (PrP C ) which is neurotoxic and amyloidogenic and induces misfolding of its physiological counterpart. The intrinsic physical characteristics of these infectious proteinaceous pathogens makes them highly resistant to the vast majority of physicochemical decontamination procedures used typically for standard disinfection. This means prions are highly persistent in contaminated tissues, the environment (surfaces) and, of great concern, on medical and surgical instruments. Traditionally, decontamination procedures for prions are tested on natural isolates coming from the brain of infected individuals with an associated high heterogeneity resulting in highly variable results. Using our novel ability to produce highly infectious recombinant prions in vitro we adapted the system to enable recovery of infectious prions from contaminated materials. This method is easy to perform and, importantly, results in highly reproducible propagation in vitro . It exploits the adherence of infectious prion protein to beads of different materials allowing accurate and repeatable assessment of the efficacy of disinfectants of differing physicochemical natures to eliminate infectious prions. This method is technically easy, requires only a small shaker and a standard biochemical technique and could be performed in any laboratory., (Copyright © 2020 Eraña, Pérez-Castro, García-Martínez, Charco, López-Moreno, Díaz-Dominguez, Barrio, González-Miranda and Castilla.)

A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease. Herein, we aimed to extend the aforementioned study on the effect of this anti-inflammatory therapy to the initial phase of scrapie, with the aim of elucidating the natural neuroinflammatory process occurring in this neurodegenerative disorder. The administration of this glucocorticoid resulted in an outstanding reduction in vacuolation and aberrant protein deposition (nearly null), and an increase in glial activation. Furthermore, evident suppression of IL-1R and IL-6 and the exacerbation of IL-1α, IL-2R, IL-10R and IFNγR were also demonstrated. Consequently, the early stage of the disease is characterized by an intact neuroglial response similar to that of healthy individuals attempting to re-establish homeostasis. A complex network of neuroinflammatory markers is involved from the very early stages of this prion disease, which probably becomes impaired in the more advanced stages. The in vivo animal model used herein provides essential observations on the pathogenesis of natural scrapie, as well as the possibility of establishing neuroglia as potential target cells for anti-inflammatory therapy.

Neuroinflammation has been correlated with the progress of neurodegeneration in many neuropathologies. Although glial cells have traditionally been considered to be protective, the concept of them as neurotoxic cells has recently emerged. Thus, a major unsolved question is the exact role of astroglia and microglia in neurodegenerative disorders. On the other hand, it is well known that glucocorticoids are the first choice to regulate inflammation and, consequently, neuroglial inflammatory activity. The objective of this study was to determine how chronic dexamethasone treatment influences the host immune response and to characterize the beneficial or detrimental role of glial cells. To date, this has not been examined using a natural neurodegenerative model of scrapie. With this aim, immunohistochemical expression of glial markers, prion protein accumulation, histopathological lesions and clinical evolution were compared with those in a control group. The results demonstrated how the complex interaction between glial populations failed to compensate for brain damage in natural conditions, emphasizing the need for using natural models. Additionally, the data showed that modulation of neuroinflammation by anti-inflammatory drugs might become a research focus as a potential therapeutic target for prion diseases, similar to that considered previously for other neurodegenerative disorders classified as prion-like diseases.

Phenotypic variability in prion diseases, such as scrapie, is associated to the existence of prion strains, which are different pathogenic prion protein (PrP Sc ) conformations with distinct pathobiological properties. To faithfully study scrapie strain variability in natural sheep isolates, transgenic mice expressing sheep cellular prion protein (PrP C ) are used. In this study, we used two of such models to bioassay 20 scrapie isolates from the Spain-France-Andorra transboundary territory. Animals were intracerebrally inoculated and survival periods, proteinase K-resistant PrP (PrP res ) banding patterns, lesion profiles and PrP Sc distribution were studied. Inocula showed a remarkable homogeneity on banding patterns, all of them but one showing 19-kDa PrP res . However, a number of isolates caused accumulation of 21-kDa PrP res in TgShp XI. A different subgroup of isolates caused long survival periods and presence of 21-kDa PrP res in Tg338 mice. It seemed that one major 19-kDa prion isoform and two distinct 21-kDa variants coexisted in source inocula, and that they could be separated by bioassay in each transgenic model. The reason why each model favours a specific component of the mixture is unknown, although PrP C expression level may play a role. Our results indicate that coinfection with more than one substrain is more frequent than infection with a single component.

Background: When pacing trains with a constant cycle length (CL) but increasing number of beats are introduced during a macroreentrant atrial tachycardia (MAT), the postpacing interval (PPI) is expected to increase if entrainment does not occur but could be stable if entrainment occurs. We tested the ability of PPI analysis to detect entrainment., Methods: Synchronized pacing trains with increasing number of beats (1-20) were delivered from the coronary sinus (CS) and lateral right atrium (RA) at a CL 20 ms shorter than the MAT CL. Pacing trains were grouped in pairs differing by one-paced beat, and the ∆PPI measured., Results: In an initial prospective cohort of 21 patients (48% had left atrial flutter) the mean ∆PPI was 21.3 ± 5.6 ms for pairs of pacing trains in which neither entrained the MAT and 2.8 ± 1.4 ms for those in which both entrained the MAT (P < .0001). Results were similar for common vs atypical flutter, PPI-TCL ≤30 ms vs PPI-TCL >30 ms, presence vs absence of antiarrhythmic drugs and faster vs slower MAT. When an index pacing train was compared to one with two-paced beats less, a PPI difference of <19 ms identified entrainment with 95% sensitivity and 98% specificity. In a validation cohort of 16 patients, this cut-off value resulted in sensitivity and specificity of 90% and 94%., Conclusions: A relatively constant ∆PPI in response to overdrive pacing with identical CL but different number of beats allows accurate discrimination between trains that entrained vs those which did not entrain a MAT., (© 2019 Wiley Periodicals, Inc.)

The analysis of the cerebrospinal fluid (CSF) biomarkers in patients with suspected prion diseases became a useful tool in diagnostic routine. Prion diseases can only be identified at clinical stages when the disease already spread throughout the brain and massive neuronal damage occurs. Consequently, the accuracy of CSF tests detecting non-symptomatic patients is unknown. Here, we aimed to investigate the usefulness of CSF-based diagnostic tests in pre-clinical and clinical naturally occurring scrapie. While decreased total prion protein (PrP) levels and positive PrP seeding activity were already detectable at pre-symptomatic stages, the surrogate markers of neuronal damage total tau (tau) and 14-3-3 proteins were exclusively increased at clinical stages. The present findings confirm that alterations in PrP levels and conformation are primary events in the pathology of prion diseases preceding neuronal damage. Our work also supports the potential use of these tests in the screening of pre-symptomatic scrapie and human prion disease cases.

While prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently demonstrated resistance to prion infection in mice overexpressing a mutated prion protein (PrP) carrying a specific amino acid substitution characteristic of canids. Here, we show that coexpression of this mutated PrP and wild-type mouse PrP in transgenic mice inoculated with different mouse-adapted prion strains (22 L, ME7, RML, and 301C) significantly increases survival times (by 45 to 113%). These data indicate that this amino acid substitution confers a dominant-negative effect on PrP, attenuating the conversion of PrP C to PrP Sc and delaying disease onset without altering the neuropathological properties of the prion strains. Taken together, these findings have important implications for the development of new treatment approaches for prion diseases based on dominant-negative proteins.

Background: Electroanatomical mapping systems have reduced the amount of fluoroscopy required to ablate the cavotricuspid isthmus. The aims of this study are to evaluate the feasibility and safety of a zero-fluoroscopy approach to cavotricuspid isthmus catheter ablation using the Carto®3 system (Biosense Webster, Diamond Bar, CA, USA) and to compare the results of this approach with those of the zero-fluoroscopy approach using the Ensite-NavX™ system (St. Jude Medical, St. Paul, MN, USA)., Methods: Twenty consecutive procedures guided by the Carto®3 system (Group A) were compared with two case-control groups matched from 146 procedures guided with the Ensite-NavX™ system. Group B consisted of 20 matched procedures from the first 50 procedures performed in the electrophysiology unit, and Group C consisted of 20 matched procedures from the last 50 procedures. Acute success (bidirectional block), complications, and recurrences were analyzed. The procedure times were also compared., Results: There were no differences in the rates of acute success (95%, 100%, and 100%, respectively), complications (0%, 5%, and 0%), and recurrences (5.2%, 0%, and 5%) in the three groups. A zero-fluoroscopy approach was attempted in all procedures, and electroanatomical mapping made it possible to successfully avoid fluoroscopy in 90% of the procedures in Group A, 85% in B, and 95% in C. The total procedure time was shorter in Group C. The fluoroscopy and radiofrequency times were not different., Conclusions: A zero-fluoroscopy approach to cavotricuspid isthmus catheter ablation using the Carto®3 system is feasible in most procedures. This approach has similar results to the zero-fluoroscopy approach using the Ensite-NavX™ system., (©2014 Wiley Periodicals, Inc.)

During the climacteric, women experience multiple health problems. As their needs are not catered for in an integral fashion due to the lack of any specific programme or mechanism to provide for this, they show an increased use of the health services, and an increased rate of referrals to different specialists. This study, carried out in a Basic Health Zone in San Fernando (Cádiz, Andalusía, Spain) on a sample of climacteric women who attended the Health Centre during 1995, examines these points and shows a significantly higher use of the health services in relation to the rest of the female population (those who are not in the climacteric age group) as well as a high percentage of referrals (74.6%) to specialists. It was found that both the level of knowledge about the climacteric and the use of the health services were influenced by the educational level (p < 0.001) and age (p < 0.05). Women who felt that their families provided an understanding and supportive attitude were found to have less psychological problems and, consequently, less consultations and referrals for this reason (p < 0.00001). The authors hope that their findings will provide a basis for the setting up of a programme of integral health care for climacteric women at the level of primary health care. With careful planning and the drawing up of a strategic plan, it would be possible to provide for the needs of this population group in a more satisfactory way, and it would also permit a rationalization of the resources available.