The 2023 Report on the Proteome from the HUPO Human Proteome Project.

Since 2010, the Human Proteome Project (HPP), the flagship initiative of the Human Proteome Organization (HUPO), has pursued two goals: (1) to credibly identify the protein parts list and (2) to make proteomics an integral part of multiomics studies of human health and disease. The HPP relies on international collaboration, data sharing, standardized reanalysis of MS data sets by PeptideAtlas and MassIVE-KB using HPP Guidelines for quality assurance, integration and curation of MS and non-MS protein data by neXtProt, plus extensive use of antibody profiling carried out by the Human Protein Atlas. According to the neXtProt release 2023-04-18, protein expression has now been credibly detected (PE1) for 18,397 of the 19,778 neXtProt predicted proteins coded in the human genome (93%). Of these PE1 proteins, 17,453 were detected with mass spectrometry (MS) in accordance with HPP Guidelines and 944 by a variety of non-MS methods. The number of neXtProt PE2, PE3, and PE4 missing proteins now stands at 1381. Achieving the unambiguous identification of 93% of predicted proteins encoded from across all chromosomes represents remarkable experimental progress on the Human Proteome parts list. Meanwhile, there are several categories of predicted proteins that have proved resistant to detection regardless of protein-based methods used. Additionally there are some PE1-4 proteins that probably should be reclassified to PE5, specifically 21 LINC entries and ∼30 HERV entries; these are being addressed in the present year. Applying proteomics in a wide array of biological and clinical studies ensures integration with other omics platforms as reported by the Biology and Disease-driven HPP teams and the antibody and pathology resource pillars. Current progress has positioned the HPP to transition to its Grand Challenge Project focused on determining the primary function(s) of every protein itself and in networks and pathways within the context of human health and disease.

Identifying PE2 and PE5 Proteins from Existing Mass Spectrometry Data Using pFind.

The Chromosome-Centric Human Proteome Project (C-HPP) aims to identify all proteins encoded by the human genome. Currently, the human proteome still contains approximately 2000 PE2-PE5 proteins, referring to annotated coding genes that lack sufficient protein-level evidence. During the past 10 years, it has been increasingly difficult to identify PE2-PE5 proteins in C-HPP approaches due to the limited occurrence. Therefore, we proposed that reanalyzing massive MS data sets in repository with newly developed algorithms may increase the occurrence of the peptides of these proteins. In this study, we downloaded 1000 MS data sets via the ProteomeXchange database. Using pFind software, we identified peptides referring to 1788 PE2-PE5 proteins. Among them, 11 PE2 and 16 PE5 proteins were identified with at least 2 peptides, and 12 of them were identified using 2 peptides in a single data set, following the criteria of the HPP guidelines. We found translation evidence for 16 of the 11 PE2 and 16 PE5 proteins in our RNC-seq data, supporting their existence. The properties of the PE2 and PE5 proteins were similar to those of the PE1 proteins. Our approach demonstrated that mining PE2 and PE5 proteins in massive data repository is still worthy, and multidata set peptide identifications may support the presence of PE2 and PE5 proteins or at least prompt additional studies for validation. Extremely high throughput could be a solution to finding more PE2 and PE5 proteins.

Enzyme replacement therapy for hypophosphatasia-The current paradigm.

Hypophosphatasia (HPP) is a rare, inherited, and systemic disorder characterized by impaired skeletal mineralization and low tissue nonspecific serum alkaline phosphatase (TNSALP) activity. It is caused by either autosomal recessive or dominant-negative mutations in the gene that encodes TNSALP. The phenotype of HPP is very broad including abnormal bone mineralization, disturbances of calcium and phosphate metabolism, pain, recurrent fracture, short stature, respiratory impairment, developmental delay, tooth loss, seizures, and premature death. Other than supportive care, there has been no disease-specific treatment available for those with HPP. Asfotase alfa is a fully humanized, recombinant enzyme replacement therapy for the management of HPP. It is available in several countries for the treatment of the more severe forms of HPP, namely perinatal and infantile HPP. This review will summarize the preclinical data on asfotase alfa and highlight the data from clinical trials and case reports. These data show the transformative nature of asfotase alfa when administered as part of an interdisciplinary treatment model.

The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults.

Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group.

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.

Exploring the problems and coping strategies of pharmacy internship in large general hospitals in China: from the perspective of preceptors.

OBJECTIVE: The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. METHODS: This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. RESULTS: Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs' perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. CONCLUSION: This study found that from the HPPs' perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.

The 2022 Report on the Human Proteome from the HUPO Human Proteome Project.

The 2022 Metrics of the Human Proteome from the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 407 (93.2%) of the 19 750 predicted proteins coded in the human genome, a net gain of 50 since 2021 from data sets generated around the world and reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 78 from 1421 to 1343. This represents continuing experimental progress on the human proteome parts list across all the chromosomes, as well as significant reclassifications. Meanwhile, applying proteomics in a vast array of biological and clinical studies continues to yield significant findings and growing integration with other omics platforms. We present highlights from the Chromosome-Centric HPP, Biology and Disease-driven HPP, and HPP Resource Pillars, compare features of mass spectrometry and Olink and Somalogic platforms, note the emergence of translation products from ribosome profiling of small open reading frames, and discuss the launch of the initial HPP Grand Challenge Project, "A Function for Each Protein".

Effects of Infantile Hypophosphatasia on Human Dental Tissue.

Hypophosphatasia (HPP) is an inherited, systemic disorder, caused by loss-of-function variants of the ALPL gene encoding the enzyme tissue non-specific alkaline phosphatase (TNSALP). HPP is characterized by low serum TNSALP concentrations associated with defective bone mineralization and increased fracture risk. Dental manifestations have been reported as the exclusive feature (odontohypophosphatasia) and in combination with skeletal complications. Enzyme replacement therapy (asfotase alfa) has been shown to improve respiratory insufficiency and skeletal complications in HPP patients, while its effects on dental status have been understudied to date. In this study, quantitative backscattered electron imaging (qBEI) and histological analysis were performed on teeth from two patients with infantile HPP before and during asfotase alfa treatment and compared to matched healthy control teeth. qBEI and histological methods revealed varying mineralization patterns in cementum and dentin with lower mineralization in HPP. Furthermore, a significantly higher repair cementum thickness was observed in HPP compared to control teeth. Comparison before and during treatment showed minor improvements in mineralization and histological parameters in the patient when normalized to matched control teeth. HPP induces heterogeneous effects on mineralization and morphology of the dental status. Short treatment with asfotase alfa slightly affects mineralization in cementum and dentin. Despite HPP being a rare disease, its mild form occurs at higher prevalence. This study is of high clinical relevance as it expands our knowledge of HPP and dental involvement. Furthermore, it contributes to the understanding of dental tissue treatment, which has hardly been studied so far.

Radial HR-pQCT and Finite Element Analysis in HPP Patients are Superior in Identifying Susceptibility to Fracture-Associated Skeletal Affections Compared to DXA and Laboratory Tests.

Hypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in the ALPL gene grouped by bone manifestations. These groups were compared by means of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) and simulated mechanical performance utilizing finite element analysis (FEA). Whereas the incidence of skeletal manifestations among the patients could not be determined by dual energy X-ray absorptiometry (DXA) or laboratory assessment, HR-pQCT evaluation showed a distinct pattern of HPP patients with such manifestations. Specifically, these patients had a pronounced loss of trabecular bone mineral density, increased trabecular spacing, and decreased ultimate force at the distal radius. Interestingly, the derived results indicate that the non-weight-bearing radius is superior to the weight-bearing tibia in identifying deteriorated skeletal patterns. Overall, the assessment by HR-pQCT appears to be of high clinical relevance due to the improved identification of HPP patients with an increased risk for fractures or other skeletal manifestations, especially at the distal radius.

The use of high pressure processing to compensate for the effects of salt reduction in ready-to-eat meat products.

Sodium chloride is an essential ingredient in meat products, where it is not only used as a flavoring agent but also to achieve desired textural properties and as an antimicrobial to improve its safety and extend shelf-life. Although NaCl plays this multi-functional role in meat products, excessive sodium intake is linked to various negative health consequences such as cardiovascular disease and obesity. Sodium chloride added to ready-to-eat meat products is the largest contributor of sodium. Thus, there is an increased interest in the development of meat products with reduced sodium levels. Strategies to reduce sodium include identification of alternatives to sodium, considering safety and functionality, and including technological innovations and alternative food processing strategies. Several studies have shown that high pressure processing (HPP) can partially compensate for the loss in functional and sensory properties of meat products as a result of NaCl reduction. This review summarizes these studies to date and will highlight the ability of HPP to enhance the safety, shelf-life and quality of sodium-reduced meat products.

Low-pressure long-time or moderate pressure pasteurization at room temperature by hyperbaric inactivation as a new nonthermal preservation approach - A case study on milk.

A new nonthermal food pasteurization approach is here presented for the first time, proposed to be called low-pressure long-time (LPLT) pasteurization or moderate pressure pasteurization (MPP) by hyperbaric inactivation (HI). To test this novel pasteurization process on raw milk, MPP by HI was carried out at three different pressure levels (150, 200 and 250 MPa), over 24 h, at naturally variable uncontrolled room temperature (≈20 °C) and compared with high pressure processing (HPP) at 600 MPa (one cycle for 90 s and a second cycle of 120 s) followed by storage under refrigeration for 21 days. Based on the results obtained, MPP at 250 MPa over 24 h caused higher microbial inactivation on total aerobic mesophiles (TAM), lactic acid bacteria (LAB) and Enterobacteriaceae (ENT) (of at least 2.2, 1.7 and 1.3 log CFU/mL, respectively) than HPP (1.1, 1.0 and 1.2 log CFU/mL, for the same microorganisms). Moreover, MPP showed a clear reduction of inoculated microorganisms to below the detection limit, in only 16 h for all pressures with reductions of at least 5.7, 5.4 and 5.5 for Listeria innocua, Salmonella senftenberg, and Escherichia coli, respectively. Additionally, during preservation under refrigeration, MPP samples (200 MPa and 250 MPa), maintained lower TAM/LAB/ENT compared to HPP, being the counts below the quantification/detection limit for at least 21 days for MPP by HI. MPP (200 MPa and 250 MPa) resulted also in counts below the detection limit for the inoculated microorganisms up to at least 21 days under refrigeration. The results of MPP by HI are very promising as a new nonthermal food pasteurization, since over 5 log reduction of vegetative bacteria were achieved, with counts maintained below the quantification/detection limit for at least 21 days under refrigeration.

Study of Inducing Factors on Resveratrol and Antioxidant Content in Germinated Peanuts.

When peanuts germinate, bioactive compounds such as resveratrol (RES), γ-aminobutyric acid (GABA), isoflavones, and polyphenol compounds are generated. Peanut kernels were germinated in the dark for two days, and stimuli including soaking liquid, rice koji, high-pressure processing (HPP), and ultrasonic treatment were tested for their ability to activate the defense mechanisms of peanut kernels, thus increasing their bioactive compound content. The results of this study indicate that no RES was detected in ungerminated peanuts, and only 5.58 µg/g of GABA was present, while unstimulated germinated peanuts contained 4.03 µg/g of RES and 258.83 µg/g of GABA. The RES content of the germinated peanuts increased to 13.64 µg/g after soaking in 0.2% phenylalanine solution, whereas a higher GABA content of 651.51 µg/g was observed after the peanuts were soaked in 0.2% glutamate. Soaking peanuts in 5% rice koji produced the highest RES and GABA contents (28.83 µg/g and 506.34 µg/g, respectively). Meanwhile, the RES and GABA contents of HPP-treated germinated peanuts (i.e., treated with HPP at 100 MPa for 10 min) increased to 7.66 µg/g and 497.09 µg/g, respectively, whereas those of ultrasonic-treated germinated peanuts (for 20 min) increased to 13.02 µg/g and 318.71 µg/g, respectively. After soaking peanuts in 0.5% rice koji, followed by HPP treatment at 100 MPa for 10 min, the RES and GABA contents of the germinated peanuts increased to 37.78 µg/g and 1196.98 µg/g, while the RES and GABA contents of the germinated peanuts treated with rice koji followed by ultrasonic treatment for 20 min increased to 46.53 µg/g and 974.52 µg/g, respectively. The flavonoid and polyphenol contents of the germinated peanuts also increased after exposure to various external stimuli, improving their DPPH free radical-scavenging ability and showing the good potential of germinated peanuts as functional products.

Application of high-pressure assisted thermal processing (PATP) at pilot scale for replacing conventional maturation and thermal cooking in whiteleg shrimp (Litopenaeus vannamei).

BACKGROUND: The aim of this work was to examine for the first time the use of high-pressure assisted thermal processing (PATP) (100, 350, 600 MPa; 100 °C; 3 min) at pilot scale for replacing shrimp (Litopenaeus vannamei) maturation and cooking, analyzing its impact on peeling yield, color, texture and sensory properties. Shrimps subjected to conventional maturation (ice; 2 days) and thermal cooking (100 °C; boiling water, 3 min) were used as controls. RESULTS: PATP treatments at 100-350 MPa improved manual peelability over the control (P ≤ 0.05), maintaining similar peeling yield, color (L*, a*, b*), texture (shear force, shear work) and sensory properties (appearance before and after peeling, flavor, firmness; P < 0.05). However, increasing pressure to 600 MPa clearly overprocessed the samples, making it impossible to remove all the meat from the shell and resulting in a softer texture, 4.1% lower peeling yield and worse sensory quality (P ≤ 0.05). CONCLUSION: PATP (< 350 MPa; 100 °C) could be an alternative to replace conventional maturation and thermal cooking in the production of cooked shrimps, reducing processing time from days to minutes by performing both processes in a single step. © 2022 Society of Chemical Industry.

Protection and guidance of downstream moving fish with horizontal bar rack bypass systems.

During their life cycle, fish carry out distinct movements within rivers and migrate upstream and downstream to reproduce, to feed, and to shelter in refuge habitats. During downstream movements, they can incur severe injuries that may be lethal directly or indirectly over time when passing through hydropower plants or when being entrained at other water intakes. Horizontal bar rack bypass systems are a state-of-the-art technology to protect and guide downstream moving fish towards a reasonably safe corridor around water intakes. They have been in operation at multiple hydropower plants for more than a decade, but only little is known about the potential fish protection and guidance efficiencies and the fine scale reactions of different fish species when encountering such racks. To resolve this, systematic live fish laboratory tests were conducted under various hydraulic conditions involving a diverse assemblage of riverine fish species differing in their swimming behavior and morphology. Six riverine species, namely spirlin (Alburnoides bipunctatus), barbel (Barbus barbus), nase (Chondrostoma nasus), brown trout (Salmo trutta fario), Atlantic salmon (Salmo salar), and European eel (Anguilla anguilla) were tested with a rack consisting of foil-shaped bars, clear bar spacings of 15 and 20 mm, a horizontal rack angle of 30° to the flow direction, and a full depth open channel bypass. Variations in fish behavior were observed between different species and hydraulic conditions, but the results suggest that the guidance and protection efficiencies primarily depend on the ratio of the fish width to the clear bar spacing. Larger fish were well protected by the horizontal bar rack, while smaller fish frequently passed through the rack. New equations are proposed to estimate the protection and guidance efficiencies as a function of the clear bar spacing and the fish species' biometry, which is highly relevant to assess the effect of horizontal bar racks as fish protection measures prior to installation.

High pressure processing (HPP) improved safety and quality of emerging aronia berry juice: a pilot scale shelf-life study.

The effect of high pressure processing (HPP, 600 MPa, 5 min) and thermal treatment (85 °C, 15 min) on aronia berry juice in a pilot scale was studied. The maximal shelf-life of treated samples at room temperature (RT, approximately 25 °C) or refrigerated storage (RS, 4 °C) was also investigated. Microbial counts, physicochemical properties, enzymes activities, phenolic compounds, and antioxidant activities of these juices were determined and compared. Results indicated that HPP treatment improved the microbial shelf-life of the aronia juice by at least 10-times at RT and 5-times at RS. Although thermal treatment was equally effective in extending the shelf-life, the high temperature resulted in a quicker degradation of polyphenols in aronia juice, which was decreased by 36.6% during RT storage (5 weeks) and 43.3% at RS storage (24 weeks). Therefore, HPP was more efficient in maintaining the safety and quality of aronia juice. The study also indicated HPP treated aronia juice could be stored at RT for at least one month that could be of benefit to the non-cold chain process which is targeting for a low-energy input while still retaining a minimal effect on the nutritional properties of food products.

Progress Identifying and Analyzing the Human Proteome: 2021 Metrics from the HUPO Human Proteome Project.

The 2021 Metrics of the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 357 (92.8%) of the 19 778 predicted proteins coded in the human genome, a gain of 483 since 2020 from reports throughout the world reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 478 to 1421. This represents remarkable progress on the proteome parts list. The utilization of proteomics in a broad array of biological and clinical studies likewise continues to expand with many important findings and effective integration with other omics platforms. We present highlights from the Immunopeptidomics, Glycoproteomics, Infectious Disease, Cardiovascular, Musculo-Skeletal, Liver, and Cancers B/D-HPP teams and from the Knowledgebase, Mass Spectrometry, Antibody Profiling, and Pathology resource pillars, as well as ethical considerations important to the clinical utilization of proteomics and protein biomarkers.

Biochemical Tools for Tracking Proteolysis.

All living organisms depend on tightly regulated cellular networks to control biological functions. Proteolysis is an important irreversible post-translational modification that regulates most, if not all, cellular processes. Proteases are a large family of enzymes that perform hydrolysis of protein substrates, leading to protein activation or degradation. The 473 known and 90 putative human proteases are divided into 5 main mechanistic groups: metalloproteases, serine proteases, cysteine proteases, threonine proteases, and aspartic acid proteases. Proteases are fundamental to all biological systems, and when dysregulated they profoundly influence disease progression. Inhibiting proteases has led to effective therapies for viral infections, cardiovascular disorders, and blood coagulation just to name a few. Between 5 and 10% of all pharmaceutical targets are proteases, despite limited knowledge about their biological roles. More than 50% of all human proteases have no known substrates. We present here a comprehensive list of all current known human proteases. We also present current and novel biochemical tools to characterize protease functions in vitro, in vivo, and ex vivo. These tools make it achievable to define both beneficial and detrimental activities of proteases in health and disease.

Clinical trials in skeletal dysplasia: a paradigm for treating rare diseases.

BACKGROUND: Genetic skeletal dysplasia conditions (GSDs) account for 5% of all birth defects. Until recently, targeted treatments were only available for select few conditions; 1 however, opportunities arising from developments in molecular diagnostic technologies are now leading to unparalleled therapeutic advances. This review explores current GSD clinical trials, their challenges and the hopes for the future. SOURCES OF DATA: A systematic literature search of relevant original articles, reviews and meta-analyses restricted to English was conducted using PubMed up to February 2020 regarding emerging GSD therapies. AREAS OF AGREEMENT: We discuss current clinical trials for in achondroplasia, osteopetrosis, osteogenesis imperfecta, hypophosphataemic rickets, hypophosphatasia and fibrous ossificans progressiva. AREAS OF CONTROVERSY: We explore challenges in GSD drug development from clinician input, cost-effectiveness and evidenced-based practice. GROWING POINTS: We explore opportunities brought by earlier diagnosis, its treatment impact and the challenges of gene editing. AREAS TIMELY FOR DEVELOPING RESEARCH: We horizon scan for future clinical trials.

Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia.

Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a decreased activity of tissue nonspecific alkaline phosphatase (TNSALP). As the onset and severity of HPP are heterogenous, it can be challenging to determine the pathogenicity of detected rare ALPL variants in symptomatic patients. We aimed to characterize patients with rare ALPL variants to propose which patients can be diagnosed with adult HPP. We included 72 patients with (1) clinical symptoms of adult HPP or positive family history and (2) low TNSALP activity and/or high pyridoxal 5'-phosphate (PLP) levels, who underwent ALPL gene sequencing. The patients were analyzed and divided into three groups depending on ALPL variant pathogenicity according to the classification of the American College of Medical Genetics and Genomics (ACMG). Reported pathogenic (n = 34 patients), rare (n = 17) and common (n = 21) ALPL variants only were found. Muscular complaints were the most frequent symptoms (> 80%), followed by bone affection (> 50%). Tooth involvement was significantly more common in patients with pathogenic or rare ALPL variants. Seven rare variants could be classified as likely pathogenic (ACMG class 4) of which five have not yet been described. Inconclusive genetic findings and less specific symptoms make diagnosis difficult in cases where adult HPP is not obvious. As not every pathogenic or rare ALPL variant leads to a manifestation of HPP, only patients with bone complications and at least one additional complication concerning teeth, muscle, central nervous and mental system, repeated low TNSALP activity and high PLP levels should be diagnosed as adult HPP if rare ALPL gene variants of ACMG class 4 or higher support the diagnosis.

The effect of oat bran consumption on gestational diabetes: a randomized controlled clinical trial.

BACKGROUND: Gestational diabetes is the most common medical complication in pregnancy, and it has many side effects for the mother and the fetus. The aim of this study was to evaluate the effect of oat bran consumption on gestational diabetes. METHODS: This study is a randomized clinical trial that was performed on 112 women with gestational diabetes treated with diet. Participants were randomly divided into two groups of 56. Participants in both groups were given a diet for gestational diabetes. In addition to the diet, the intervention group received 30 g of oat bran daily for 4 weeks at lunch and dinner. Tests of fasting blood glucose and two-hour postprandial (2hpp) glucose were taken from both groups: before the intervention, and 2 and 4 weeks after the start of the intervention. Data analysis was performed using SPSS statistical software (version 22) using independent t-test, as well as Chi-square and Mann-Whitney tests. P values less than 0.05 were considered statistically significant. RESULTS: There was no statistically significant difference between the two groups in terms of mean blood glucose before the intervention, while 2 and 4 weeks after the intervention, mean fasting blood glucose and two-hour postprandial (2hpp) glucose decreased significantly in the intervention group compared with the control group (P < 0.001). CONCLUSION: Based on the results of this study, the addition of oat bran to the standard diet for pregnant women with gestational diabetes reduced fasting blood glucose and two-hour postprandial (2hpp) glucose. More detailed studies with higher sample sizes are recommended to prove the effectiveness of this valuable dietary supplement. TRIAL REGISTRATION: IRCT registration number: IRCT20191220045828N1 . Registration date: 2020-04-18. Registered while recruiting.