Awake bruxism behaviors frequency in a group of healthy young adults with different psychological scores.

OBJECTIVE: To assess the frequency of awake bruxism (AB) behaviors in a group of undergraduate dentistry students and correlate it with the status of anxiety and depression. MATERIALS AND METHODS: The frequency of five oral behaviors (i.e., relaxed jaw muscle, teeth contact, mandible bracing, teeth clenching, teeth grinding) was evaluated using a smartphone-based ecological momentary assessment (EMA) approach. The anxiety and depression status was investigated with the four-item patient health questionnaire for anxiety and depression (PHQ-4). ANOVA with Tukey post-hoc test was used to assess the difference in frequency of AB behaviors among the four PHQ-4 groups. RESULTS: Among the four groups, there was a statistically significant difference in the frequency of relaxed jaw muscle, teeth contact, mandible bracing, and teeth clenching, but not for teeth grinding. CONCLUSION: Based on this cross-sectional study's findings, psyche seems to have a determinant impact on AB behaviors, which is significantly higher in individuals with anxiety and depression traits.

Correlation between bilateral TMJ MRI findings: A systematic review of the literature.

The correlation between magnetic resonance imaging (MRI) signs and clinical findings has been highlighted in multiple studies. However, very little information is available on the correlation between the bilateral temporomandibular joints (TMJs) of the same individual. The majority of efforts in the clinical research setting have focused on the correlation between ipsilateral imaging and clinical findings, while less attention has been paid to the contralateral imaging findings of the anatomical structures.The objective of this paper was to review the existing literature that compares temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings from both sides of the same individual.In January 2024, a systematic search of the literature from major search engines (MEDLINE (PubMed), Scopus) was conducted to identify all peer-reviewed English-language studies that presented an MRI comparison of left and right TMJ data in the same patients. The articles were analyzed using a Population/ Intervention/Comparison/Outcome (PICO) format.The search terms "temporomandibular joint" AND "magnetic" AND "resonance" yielded 2,561 results. Only 2 papers met the established inclusion criteria. The results of the papers included in the systematic review were not comparable due to differences in the evaluation of the TMJs, which prevented a meta-analysis. Manfredini et al. identified a statistical correlation between disc displacement, osseous changes (OC) and joint effusion (JE) between the joints of the contralateral sides. Koca et al. observed a significant difference in TMJ MRI findings between the painful and non-painful sides of each individual in a bruxism group and a control group (p = 0.001, p < 0.001 and p = 0.004, p < 0.001, respectively).The studies on the correlation between the right and left TMJs remain scarce. A comparative analysis of the 2 sides of the TMJ in individual patients is rarely reported.The review did not identify a common result for the findings of the contralateral TMJs in the 2 articles included.

A Pathophysiological Approach to Spontaneous Orbital Meningoceles: Case Report and Systematic Review.

BACKGROUND: Spontaneous orbital cephaloceles are a rare condition. The purpose of this study is to provide a description of a clinical case and to carry out a systematic literature review. METHODS: A systematic review of the English literature published on the Pubmed, Scopus, and Web of Science databases was conducted, according to the PRISMA recommendations. RESULTS: A 6-year-old patient was admitted for right otomastoiditis and thrombosis of the sigmoid and transverse sinuses, as well as the proximal portion of the internal jugular vein. Radiological examinations revealed a left orbital mass (22 × 14 mm) compatible with asymptomatic orbital meningocele (MC) herniated from the superior orbital fissure (SOF). The child underwent a right mastoidectomy. After the development of symptoms and signs of intracranial hypertension (ICH), endovascular thrombectomy and transverse sinus stenting were performed, with improvement of the clinical conditions and reduction of the orbital MC. The systematic literature review encompassed 29 publications on 43 patients with spontaneous orbital MC. In the majority of cases, surgery was the preferred treatment. CONCLUSIONS: The present case report and systematic review highlight the importance of ICH investigation and a pathophysiological-oriented treatment approach. The experiences described in the literature are limited, making the collection of additional data paramount.

Endovascular coils extrusion after internal carotid artery occlusion: From management to follow-up.

KEY POINTS: ICA coil extrusion (ICA-CE) occurs most frequently in the nasopharyngeal/sinonasal site. Evaluating the ICA coils stability, through an angiography, is of primary importance. ICA-CE management needs to be decided based on the patient's symptoms and general status.

Front-Line Therapeutic Strategy in Metastatic Hormone Sensitive Prostate Cancer: An Updated Therapeutic Algorithm.

Prostate carcinoma (PC), the second most diagnosed cancer globally, saw approximately 1,414,000 new cases in 2020, with 17% being de novo metastatic. In these cases, the 5-year relative survival rate is 32%. Metastatic hormone-sensitive prostate cancer (mHSPC) includes those with metastatic disease at initial diagnosis or after initial therapy without long-term androgen deprivation therapy (ADT), eventually progressing to castration-resistant prostate cancer (CRPC). The established therapeutic principle of ADT has persisted for 80 years, with luteinizing hormone-releasing hormone (LHRH) agonists like leuprorelin being commonly used. LHRH antagonists, such as degarelix, have also emerged. Recent advances in mHSPC treatment involve combination strategies with drugs proven effective in CRPC, considering prognostic factors like disease volume and presentation. This review outlines pivotal trials leading to drug approvals in mHSPC and proposes a treatment decision algorithm for the same, based on statement from the Tuscan Interdisciplinary Uro-Oncological Group. A multidisciplinary approach is crucial to tailor treatment intensity and weigh risks and benefits effectively.

A randomized controlled clinical trial on press and block lithium disilicate partial crowns: A 4-year recall.

PURPOSE: To evaluate clinical performances of two lithium disilicate systems (Initial LiSi press vs Initial LiSi Block, GC Co.) using modified United States Public Health Service (USPHS) evaluation criteria and survival rates after 4 years of clinical service. METHODS: Partial adhesive crowns on natural abutment posterior teeth were made on 60 subjects who were randomly divided into two groups: Group 1: Initial LiSi press and Group 2: Initial LiSi Block. Fabrication of partial crowns was made with full analog and digital procedure in Groups 1 and 2 respectively. The restorations were followed-up for 1 and 4 years, and the modified USPHS evaluation was performed at baseline and each recall together with periodontal evaluation. Contingency tables to assess for significant differences of success over time in each group and time-dependent Cox regression to test for differences between the two groups were used and the level of significance was set at P< 0.05. RESULTS: Regarding modified USPHS scores, all evaluated parameters showed Alpha or Bravo and no Charlie was recorded. No statistically significant difference emerged between the two groups in any of the assessed variables (P> 0.05). No statistically significant difference between scores recorded at the baseline and each recall. All modified USPHS scores were compatible with the outcome of clinical success and no one restoration was replaced or repaired, and the survival rate was 100% after 4 years of clinical service. No difference was found between traditional and digital procedure to fabricate the crowns. The two lithium disilicate materials showed similar results after 4 years of clinical service. CLINICAL SIGNIFICANCE: The crowns made with the two tested lithium disilicate materials with analog and digital procedures showed 100% survival after 4 years of clinical service with no statistically significant difference using the modified USPHS scores.

Association of Acidotolerant Cyanobacteria to Microbial Mats below pH 1 in Acidic Mineral Precipitates in Río Tinto River in Spain.

This report describes acidic microbial mats containing cyanobacteria that are strongly associated to precipitated minerals in the source area of Río Tinto. Río Tinto (Huelva, Southwestern Spain) is an extreme acidic environment where iron and sulfur cycles play a fundamental role in sustaining the extremely low pH and the high concentration of heavy metals, while maintaining a high level of microbial diversity. These multi-layered mineral deposits are stable all year round and are characterized by a succession of thick greenish-blue and brownish layers mainly composed of natrojarosite. The temperature and absorbance above and below the mineral precipitates were followed and stable conditions were detected inside the mineral precipitates. Different methodologies, scanning and transmission electron microscopy, immunological detection, fluorescence in situ hybridization, and metagenomic analysis were used to describe the biodiversity existing in these microbial mats, demonstrating, for the first time, the existence of acid-tolerant cyanobacteria in a hyperacidic environment of below pH 1. Up to 0.46% of the classified sequences belong to cyanobacterial microorganisms, and 1.47% of the aligned DNA reads belong to the Cyanobacteria clade.

Trueness and precision of an intraoral scanner on abutments with subgingival vertical margins: An in vitro study.

OBJECTIVES: This study aimed to evaluate the accuracy of an intraoral scanner (IOS - Medit i700) on tooth abutments with vertical preparations at 2 depths below the free gingival margin, and to determine if the IOS can reproduce the area beyond the finish surface of the tested preparation geometry. METHODS: Two abutments for a maxillary first molar were designed by means of CAD software, with vertical preparations set at 1 and 2 mm below the gingiva. These abutments were subsequently printed in resin and placed on a reference model. The reference files consisted of scans made using a metrological machine on these abutments. Ten scans were made with the tested IOS on each sample, resulting in two study groups. The scans from the experimental groups were labeled "V-1″ for vertical preparation at 1 mm below the gingival margin and "V-2″ for 2 mm below. The analysis of these scans was performed using Geomagic Control X (3D SYSTEMS) to assess their trueness and precision in µm. Descriptive statistics with a 95 % confidence interval were employed, alongside independent sample tests, to ascertain any differences between the groups (α=0.05). RESULTS: Statistically significant differences were not found both for trueness (p=.104) and precision (p=.409), between the tested geometries. The mean values for trueness were V-1 = 37.5[31.4-43.6]; V-2 = 32.6[30.6-34.6]. About the precision, the mean values were V-1 = 20.5[8.4-32.5]; V-2 = 18.4[8.2-28.5]. In both the study groups, it was possible to detect the surface beyond the finish area. CONCLUSIONS: Within the limitations of this study, vertical preparation design allows for registration of the tooth anatomy beyond the finish area with IOS. Moreover, the mean accuracy values were clinically acceptable at both 1 and 2 mm below the gingival margin.

Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

CT and MR anatomy of the larynx and hypopharynx.

Imaging of the larynx and hypopharynx is frequently requested to assess the extent of neoplasms beyond the field of view of endoscopic evaluation. The combination of optical and cross-sectional imaging allows tumors to be classified according to AJCC/UICC guidelines. A thorough understanding of laryngeal and hypopharyngeal anatomy is crucial to guide the radiological eye along the possible pathways of the spread of diseases and to guide differential diagnoses. Computed tomography (CT) has been the first cross-sectional imaging technique used to evaluate the larynx and hypopharynx; its spatial resolution combined with volumetric capability and the use of injectable contrast medium made CT the working horse in the assessment of neoplastic and inflammatory diseases. In the last two decades, magnetic resonance (MR) supported CT in the most challenging cases, when the optimal contrast resolution due to the multisequence portfolio is needed to assess the neoplastic involvement of laryngeal cartilages, paraglottic space(s), and extra laryngeal spread. The aim of this paper is to give a comprehensive radiological overview of larynx and hypopharynx complex anatomy, combining in vivo images, anatomical sections, and images of ex vivo specimens.

A peripheral blood mononuclear cell-based in vitro model: A tool to explore indoleamine 2, 3-dioxygenase-1 (IDO1).

BACKGROUND: Proinflammatory cytokines powerfully induce the rate-limiting enzyme indoleamine 2, 3-dioxygenase-1 (IDO-1) in dendritic cells (DCs) and monocytes, it converts tryptophan (Trp) into L-kynurenine (KYN), along the kynurenine pathway (KP). This mechanism represents a crucial innate immunity regulator that can modulate T cells. This work explores the role of IDO1 in lymphocyte proliferation within a specific pro-inflammatory milieu. METHODS: Peripheral blood mononuclera cells (PBMCs) were isolated from buffy coats taken from healthy blood donors and exposed to a pro-inflammatory milieu triggered by a double-hit stimulus: lipopolysaccharide (LPS) plus anti-CD3/CD28. The IDO1 mRNA levels in the PBMCs were measured by RT-PCR; the IDO1 activity was analyzed using the KYN/Trp ratio, measured by HPLC-EC; and lymphocyte proliferation was measured by flow cytometry. Trp and epacadostat (EP) were used as an IDO1 substrate and inhibitor, respectively. KYN, which is known to modulate Teffs, was tested as a positive control in lymphocyte proliferation. RESULTS: IDO1 expression and activity in PBMCs increased in an in vitro pro-inflammatory milieu. The lymphoid stimulus increased IDO1 expression and activity, which supports the interaction between the activated lymphocytes and the circulating myeloid IDO1-expressing cells. The addition of Trp decreased lymphocyte proliferation but EP, which abrogated the IDO1 function, had no impact on proliferation. Additionally, incubation with KYN seemed to decrease the lymphocyte proliferation. CONCLUSION: IDO1 inhibition did not change T lymphocyte proliferation. We present herein an in vitro experimental model suitable to measure IDO1 expression and activity in circulating myeloid cells.

Muscle Oximetry in Sports Science: An Updated Systematic Review.

BACKGROUND: In the last 5 years since our last systematic review, a significant number of articles have been published on the technical aspects of muscle near-infrared spectroscopy (NIRS), the interpretation of the signals and the benefits of using the NIRS technique to measure the physiological status of muscles and to determine the workload of working muscles. OBJECTIVES: Considering the consistent number of studies on the application of muscle oximetry in sports science published over the last 5 years, the objectives of this updated systematic review were to highlight the applications of muscle oximetry in the assessment of skeletal muscle oxidative performance in sports activities and to emphasize how this technology has been applied to exercise and training over the last 5 years. In addition, some recent instrumental developments will be briefly summarized. METHODS: Preferred Reporting Items for Systematic Reviews guidelines were followed in a systematic fashion to search, appraise and synthesize existing literature on this topic. Electronic databases such as Scopus, MEDLINE/PubMed and SPORTDiscus were searched from March 2017 up to March 2023. Potential inclusions were screened against eligibility criteria relating to recreationally trained to elite athletes, with or without training programmes, who must have assessed physiological variables monitored by commercial oximeters or NIRS instrumentation. RESULTS: Of the identified records, 191 studies regrouping 3435 participants, met the eligibility criteria. This systematic review highlighted a number of key findings in 37 domains of sport activities. Overall, NIRS information can be used as a meaningful marker of skeletal muscle oxidative capacity and can become one of the primary monitoring tools in practice in conjunction with, or in comparison with, heart rate or mechanical power indices in diverse exercise contexts and across different types of training and interventions. CONCLUSIONS: Although the feasibility and success of the use of muscle oximetry in sports science is well documented, there is still a need for further instrumental development to overcome current instrumental limitations. Longitudinal studies are urgently needed to strengthen the benefits of using muscle oximetry in sports science.

Molecular Modeling of the Adsorption of an Egg Yolk Protein on a Water-Oil Interface.

Egg yolk contains several molecular species with emulsifying properties, such as proteins and phospholipids. In particular, these molecules have both polar and nonpolar parts and thus can act as surfactants. One of the most surface-active proteins from egg yolk low-density lipoproteins is the so-called Apovitellenin-1. Experimental studies have been hindered by difficulties in isolating individual species from egg yolk lipoproteins. The purpose of this work was to assess the emulsifying properties of Apovitellenin-1 and any potential cooperative or competitive behavior in the presence of phospholipids. To do so, molecular simulations were carried out in a liquid-liquid interfacial system consisting of water and soybean oil, with varying concentrations of phospholipids and for different spatial configurations. To evaluate the conformational stability of the protein at the water-oil interface, the Gibbs free energy was computed from Metadynamics simulations as a function of the distance from the interface and of the radius of gyration. Moreover, a detailed analysis was also performed to determine which peptide residues were responsible for the protein adsorption at the oil-water interface as well as the lowering of the interfacial tension. Lastly, we combined the simulation results with a thermodynamic model to predict the interfacial tension behavior at increasing protein bulk concentration, which cannot be measured experimentally.

Side-door temporoparietal fascia flap: First experience with a novel technique for anterior skull base reconstruction.

BACKGROUND: Modern achievements in transnasal endoscopic skull base (SB) surgery have led to complex resections that render reconstruction a challenge. Temporoparietal fascia flap (TPFF) is a suitable option for SB reconstruction. The side-door TPFF technique for anterior SB reconstruction is described here for the first time in a real-life surgical setting. METHODS: Patients affected by a SB malignancy who underwent cranioendoscopic resection were included. For reconstruction, a multilayer reconstruction technique including side-door TPFF transposition was employed. RESULTS: TPFF transposition was performed in five patients. The TPFF could be easily transposed via a side-door approach. It adequately covered the edges of the defect and supported optimal healing of the surgical site. During follow-up, vitality and integration of the TPFF were assessed endoscopically and radiologically. CONCLUSIONS: The TPFF side-door transposition technique is a valuable option in anterior SB reconstruction that can provide fast and effective healing, especially in patients needing adjuvant radiotherapy.

The treatment of advanced melanoma: Current approaches and new challenges.

In recent years, advances in melanoma treatment have renewed patient hope. This comprehensive review emphasizes the evolving treatment landscape, particularly highlighting first-line strategies and the interplay between immune-checkpoint inhibitors (ICIs) and targeted therapies. Ipilimumab plus nivolumab has achieved the best median overall survival, exceeding 70 months. However, the introduction of new ICIs, like relatlimab, has added complexity to first-line therapy decisions. Our aim is to guide clinicians in making personalized treatment decisions. Various features, including brain metastases, PD-L1 expression, BRAF mutation, performance status, and prior adjuvant therapy, significantly impact the direction of advanced melanoma treatment. We also provide the latest insights into the treatment of rare melanoma subtypes, such as uveal melanoma, where tebentafusp has shown promising improvements in overall survival for metastatic uveal melanoma patients. This review provides invaluable insights for clinicians, enabling informed treatment choices and deepening our understanding of the multifaceted challenges associated with advanced melanoma management.

Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

Objective Non-Invasive Bio-Parametric Evaluation of Regenerated Skin: A Comparison of Two Acellular Dermal Substitutes.

Several dermal substitutes are available on the market, but there is no precise indication that helps surgeons choose the proper one. Few studies have tried to compare different xenogeneic bioengineered products, but no objective bio-parametric comparison has been made yet. Fifteen patients who underwent skin reconstruction with Integra® or Pelnac® were retrospectively evaluated. After at least 12 months of follow-up, an objective and quantitative assessment of several skin biophysical properties, such as color, texture, elasticity, hydration, glossiness and trans-epidermal water loss, were measured with non-invasive skin measurement devices. The grafted skin showed a reduction of the superficial hydration level and a tendency to lower values of trans-epidermal water loss with both dermal substitutes. Melanic and hemoglobin pigmentation were higher in comparison to the donor site in both groups, while a melanic pigmentation increase versus the surrounding skin was seen just with Integra®. Finally, the skin was found to be more elastic when reconstructed with Integra®. The skin barrier appeared to be intact in both groups. Hence, these substitutes are valuable means of skin regeneration. Integra® seems to be more advantageous for reconstructing areas that need more skin flexibility.

Nasoseptal flap with extended pedicle dissection based on the maxillary artery: Clinical series of 55 cases.

KEY POINTS: Nasoseptal flap with extended pedicle dissection is a low morbidity and high success rate flap. It is a flap that can be applied to reconstruct a wide range of ipsilateral skull base defects.

Multifactorial action of lavender and lavandin oils against filamentous fungi.

AIMS: In this study, five essential oils (EOs) from different species of Lavandula hybrida abrialis, for Lavandula hybrida R.C., Lavandula hybrida 'super A', Lavandula hybrida 'super Z' and Lavandula vera and its hybrids Lavender were evaluated against 26 dust-isolated fungal strains from North Africa. METHODS AND RESULTS: The composition of the different EOs was determined from volume to dry weight. The photochemical analyses were performed via gas chromatography (GC). The cytotoxic effect of five lavender EOs on human epithelial colorectal adenocarcinoma cells (Caco-2) cell line was done. A total of 26 strains of filamentous fungi including Aspergillus spp., Botrytis cinerea, Ceriporia spp., Fusarium spp. and Penicillium glabrum were isolated from sand dust samples via molecular diagnostic tool of PCR. Fungal strains with the lowest minimal lethal concentration (MLC) were Penicillium glabrum, Ceriporia spp. and a strain of Aspergillus spp. CONCLUSIONS: More studies are needed to verify the activity of this EO against more different fungal species, and determine the active ingredients.Significance and impact of study: MIC of the antifungal efficacy relating to EOs was evaluated. The EOs tests showed no cytotoxic effect at very low concentrations, ranging from 0.03% (IC50 0.9132 mg/mL) (L. hybrid Abrialis) to 0.001% (IC50 1.631 mg/mL) (L. hybrid R.C.).

Chewing performance of patients with worn dentition before and after restorations: A scoping review.

BACKGROUND: Tooth wear is a multifactorial complex process related to the loss of dental tissue, due to chemical or mechanical processes, by abrasion, attrition, erosion. Restorative treatment represents an attempt to rebuild and recreate the lost structure. OBJECTIVE: This scoping review aims to investigate whether restorative treatment of worn dentition (either with direct or indirect adhesive composite adhesive procedures or with prosthetic techniques) can have an impact on the masticatory performance parameters. METHODS: A scoping review was conducted on multiple databases (Pubmed, Medline CENTRAL, ICTRP), following the PRISMA guidelines. Abstracts of research papers were screened for suitability, and full-text articles were obtained for those who satisfied the inclusion and exclusion criteria. RESULTS: Only one article meet the inclusion criteria of the review. Restorative treatment of worn dentition although have a positive impact on the self-report ability to chew, has no effect on the masticatory performance test. CONCLUSION: At the moment, not enough evidence to comment on the actual therapeutic role of restorative treatment on tooth wear is available. Clinicians, before taking any clinical decision, should carefully discuss with patients the needs and expectations of the treatment plan.