Implications of chronic moderate protein-deficiency malnutrition on doxorubicin pharmacokinetics and cardiotoxicity in early post-weaning stage.

BACKGROUND: Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer patients is well documented. However, despite being a more prevalent and distinct entity, moderate malnutrition is until now unexplored for its effects on treatment outcomes. AIMS: In this study we aimed to investigate the molecular basis of altered pharmacokinetics and cardiotoxicity of doxorubicin observed in early-life chronic moderate protein deficiency malnutrition. MATERIALS AND METHODS: We developed an animal model of early-life moderate protein-deficiency malnutrition and validated it using clinical samples. This model was used to study pharmacokinetic and toxicity changes and was further utilized to study the molecular changes in liver and heart to get mechanistic insights. KEY FINDINGS: Here we show that moderate protein-deficiency malnutrition in weanling rats causes changes in drug disposition in the liver by modification of hepatic ABCC3 and MRP2 transporters through the TNFα signalling axis. Furthermore, malnourished rats in repeat-dose doxorubicin toxicity study showed higher toxicity and mortality. A higher accumulation of doxorubicin in the heart was observed which was associated with alterations in cardiac metabolic pathways and increased cardiotoxicity. SIGNIFICANCE: Our findings indicate that moderate malnutrition causes increased susceptibility towards toxic side effects of chemotherapy. These results may necessitate further investigations and new guidelines on the dosing of chemotherapy in moderately malnourished pediatric cancer patients.

D-Bifunctional Protein Deficiency Diagnosis-A Challenge in Low Resource Settings: Case Report and Review of the Literature.

D-bifunctional protein deficiency (D-BPD) is a rare, autosomal recessive peroxisomal disorder that affects the breakdown of long-chain fatty acids. Patients with D-BPD typically present during the neonatal period with hypotonia, seizures, and facial dysmorphism, followed by severe developmental delay and early mortality. While some patients have survived past two years of age, the detectable enzyme activity in these rare cases was likely a contributing factor. We report a D-BPD case and comment on challenges faced in diagnosis based on a narrative literature review. An overview of Romania's first patient diagnosed with D-BPD is provided, including clinical presentation, imaging, biochemical, molecular data, and clinical course. Establishing a diagnosis can be challenging, as the clinical picture is often incomplete or similar to many other conditions. Our patient was diagnosed with type I D-BPD based on whole-exome sequencing (WES) results revealing a pathogenic frameshift variant of the HSD17B4 gene, c788del, p(Pro263GInfs*2), previously identified in another D-BPD patient. WES also identified a variant of the SUOX gene with unclear significance. We advocate for using molecular diagnosis in critically ill newborns and infants to improve care, reduce healthcare costs, and allow for familial counseling.

Steroidogenic acute regulatory protein (STAR) deficiency: Our experience and systematic review for phenotype-genotype correlation.

OBJECTIVE: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia). RESULTS: We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A. CONCLUSIONS: We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH.

Revolutionizing Personalized Protein Energy Malnutrition Treatment: Harnessing the Power of Chat GPT.

Protein energy malnutrition (PEM) is a global public health concern, and personalized treatment approaches are crucial for improved outcomes. This study explores the transformative potential of Chat GPT, an AI language model, in revolutionizing personalized treatment for PEM. By providing accurate information, personalized dietary recommendations, food choices, psychological counseling of the patient and real-time monitoring and support, Chat GPT can enhance the effectiveness of PEM interventions. Along with the benefits it is also important to acknowledge its potential flaws and limitations. The study emphasizes the importance of collaboration between AI technology and healthcare professionals to leverage Chat GPT's capabilities effectively. By combining human expertise with AI capabilities, personalized PEM treatment can be revolutionized, leading to improved patient outcomes and a comprehensive approach to addressing this global public health concern. The study highlights the significant impact of Chat GPT in providing tailored guidance and continuous support throughout the treatment process, empowering individuals and improving their overall well-being.

Rare forms of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal steroidogenesis. Although 21-hydroxylase, 11ß-hydroxylase, 3ß-hydroxysteroid dehydrogenase type 2, 17α-hydroxylase/17,20-lyase, P450 oxidoreductase, steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme deficiencies are considered within the definition of CAH, the term 'CAH' is often used to refer to '21-hydroxylase deficiency (21OHD)' since 21OHD accounts for approximately 95% of CAH in most populations. The prevalence of the rare forms of CAH varies according to ethnicity and geographical location. In most cases, the biochemical fingerprint of impaired steroidogenesis points to the specific subtypes of CAH, and genetic testing is usually required to confirm the diagnosis. Despite there are significant variations in clinical characteristics and management, most data about the rare CAH forms are extrapolated from 21OHD. This review article aims to collate the currently available data about the diagnosis and the management of rare forms of CAH.

Impact of protein deficient diet on the pharmacokinetics of glibenclamide in a model of malnutrition in rats.

Purpose: The present investigation deals with the impact of protein energy malnourished condition on the pharmacokinetic profile of glibenclamide. Protein energy malnourished condition leads to malnutrition related diabetes mellitus (MRDM), Fibrocalculus pancreatic diabetes mellitus (FCPD) or Lean body mass diabetes mellitus (LBMDM). Method: In the present study, malnutrition was developed in female wistar rats using a modified protein deficient diet (0.5%). The experiment was performed on 12 animals, each group containing 6 female wistar rats. The control group animals were fed with standard pellet diet (AIN 93 G diet) while group 2 received the low protein diet (0.5%) for 75 days. Glibenclamide (Gli) suspension (30 mg/kg) was administered orally to these rats on 75 days and kinetic parameters were evaluated by HPLC analysis.The pharmacokinetic interpretation done by pksolver software version 2.0, statistical comparison done by applying student T test. Results: The results of body weight and hematological parameters indicated a significant decreased in the body weight in protein deficit rats to 124.1 ± 6.2 g compared to 235.5 ± 8.4 g (p < 0.01) control rats; whereas a decrease in the hemoglobin to 5.8 ± 0.6 g/dL, total blood protein level to 6.9 ± 0.6 g/dL and blood albumin levels to 2.7 ± 0.4 g/dL in protein deficit rats compared to 15 ± 0.7 g/dL(p < 0.05), 8.1 ± 0.4 g/dL(p < 0.05), and 4.5 ± 0.2 g/dL(p < 0.05), respectively in control rats. All these findings reflect the malnourished condition and weight loss due to a protein deficit diet in experimental animals. There was an increase in the fasting blood glucose levels up to 150 ± 17.4 mg/dL in the protein deficit diet group as compared to 98.7 ± 14.1 mg/dL(p < 0.05) in control rats reflect the prediabetes state in malnourished animals. The results of the pharmacokinetic study reflect a significant lowering of half-life (T½) of glibenclamide to 96.8 ± 0.8 min. in malnourished rats compared to 166.7 ± 0.74 min. (p < 0.001) in control rats. The maximum concentration (Cmax) of glibenclamide in the malnourished rats was significantly higher 20.74 ± 0.65 µg/mL and also took double time i.e. about 180 min. to reach maximum concentration (Tmax) compared to the control rats values 7.9 ± 0.84 µg/mL (p < 0.001) and 90.0 ± 0.24 min. (p < 0.001) respectively. The area under the plasma concentration-time curve [AUC(0-∞)] in malnourished rats increased 4439.1 ± 40.6 µg/ml*min as compared to 1235.9 ± 55.8 µg/ml*min (p < 0.001) in control rats. There was a lowering in the total body clearance (CL) to 0.4 ± 0.02 L/hr and volume of distribution (Vd) to 1.75 ± 0.07 L of glibenclamide in the protein deficit group compared to 1.4 ± 0.3 L/hr (p < 0.001) and 3.14 ± 0.8 L (p < 0.01), respectively in the control rats. Conclusion: From this study it concludes that there is an increase in the T½, Cmax, Tmax and AUC(0-∞) of glibenclamide in malnourished rats while the total body clearance and volume of distribution is lowered. Therefore this study proposes to conduct an adequate pharmacokinetic study in malnourished patients to decide whether the standard glibenclamide dose should be adapted according to the nutritional status of the individual.

Effect of perinatal dietary protein deficiency on some neurochemicals and cytoarchitectural balance, in F1 and F2 generations of rats.

ABSTRACTProtein deficiency, characterized by an inadequate intake of protein in the diet that fails to meet the body's physiological requirements across various stages, can lead to detrimental outcomes. This is of interest due to the persistent low protein content in staple foods and suboptimal dietary patterns. The study sought to assess the intergenerational repercussions of dietary protein deficiency on specific neurochemicals and the cytoarchitecture of the brain within the F1 and F2 generations of rats. The rats were categorized into four groups based on the protein content percentage in their diets: 21% protein diet (21%PD), 10% protein diet (10%PD), 5% protein diet (5%PD), and control diet. Neurobehavior was assessed, while brain serotonin and dopamine levels were measured using HPLC. BDNF and GDNF expression in the hippocampal and prefrontal (PFC) sections, Immunohistochemical investigations of the morphological impact on the hippocampus and PFC, were also analyzed. The protein-deficient groups displayed anxiety, loss of striatal serotonin and increased dopamine levels, degenerated pyramidal cells in the hippocampus, and a prominent reduction in cellular density in the PFC. BDNF and GDNF levels in the PFC were reduced in the 5%PD group. GFAP astrocyte expression was observed to be increased in the prefrontal cortex (PFC) and hippocampal sections, indicating heightened reactivity. The density of hypertrophied cells across generations further suggests the presence of neuroinflammation. Changes in brain structure, neurotransmitter levels, and neurotrophic factor levels may indicate intergenerational alterations in critical regions, potentially serving as indicators of the brain's adaptive response to address protein deficiency across successive generations.

Prevalencia y factores relacionados con desnutrición en la primera infancia. Colombia año 2018 a 2020

La desnutrición como enfermedad de origen social es la expresión última de la situación de inseguridad alimentaria y nutricional de una población, al afectar principalmente a los niños. El objetivo fue analizar la prevalencia y factores relacionados con la desnutrición en la primera infancia en Colombia durante los años 2018 a 2020, mediante un estudio cuantitativo descriptivo de tipo ecológico - exploratorio, con recolección de datos retrospectivos a partir de reportes obtenidos del Sistema Integrado de Información de la Protección Social. El total de casos corresponde a 43.823 reportes, la prevalencia para los tres años fue de 1,13% principalmente en los departamentos de Guajira (n: 3.488; 3,17%) y Boyacá (n: 1.277; 1,39%), mayor número de casos presentados en el sexo masculino (n: 23.804; 54,3%), en edad entre 0 y 1 año (n: 17.099; 39,0%), pertenecientes al régimen subsidiado (n: 28.814; 65,75%) y ubicados en la cabecera municipal (n: 28.114; 64,15%). Con relación a la pertenencia étnica la mayor frecuencia se evidencia en "otras etnias" (n: 33.050; 75,42%), seguido de la etnia indígena (n: 8.348; 19,05%) y el estrato socioeconómico más representativo es el "bajo-bajo" (n: 17.620; 40,21%). Además, existe relación entre el sexo masculino y la desnutrición, comportándose como un factor de riesgo, y el vivir en centro poblado disminuye la probabilidad de presentar desnutrición. Se evidenció una frecuencia significativa de características asociadas a los determinantes sociales en salud y variables específicas relacionadas con la desnutrición.

Malnutrition as a disease of social origin is the ultimate expression of the situation of food and nutritional insecurity of a population, mainly affecting children. The objective was to analyze the prevalence and factors related to malnutrition in early childhood in Colombia during the years 2018 to 2020, through a descriptive quantitative study of an ecological-exploratory type, with retrospective data collection from reports obtained from the Integrated System of Social Protection Information. The total number of cases corresponds to 43,823 reports, the prevalence for the three years was 1.13%, mainly in the departments of Guajira (n: 3,488; 3.17%) and Boyacá (n: 1,277; 1.39%). greater number of cases presented in males (n: 23,804; 54.3%), aged between 0 and 1 year (n: 17,099; 39.0%), belonging to the subsidized regime (n: 28,814; 65.75%) and located in the municipal seat (n: 28,114; 64.15%). In relation to ethnicity, the highest frequency is evidenced in "other ethnic groups" (n: 33,050; 75.42%), followed by the indigenous ethnic group (n: 8,348; 19.05%), and the most representative socioeconomic stratum is the "low-low" (n: 17,620; 40.21%). In addition, there is a relationship between the male sex and malnutrition, behaving as a risk factor, and living in a populated center decreases the probability of presenting malnutrition. A significant frequency of characteristics associated with the social determinants of health and specific variables related to malnutrition was evidenced.

Mismatch repair protein deficiency in endometriosis: Precursor of endometriosis-associated ovarian cancer in women with lynch syndrome.

OBJECTIVE: We aimed to elucidate the pathogenesis of ovarian cancer through the loss of mismatch repair (MMR) proteins in women with Lynch syndrome (LS) in this report. CASE REPORT: Two women with LS underwent surgery for synchronous endometrial cancer and ovarian cancer. In both cases, immunohistochemical examination showed concomitant MMR protein deficiency in endometrial cancer, ovarian cancer, and contiguous ovarian endometriosis. In Case 1, the macroscopically normal ovary included multiple endometrioses with MSH2 and MSH6 expression, and FIGO grade 1 endometrioid carcinoma and contiguous endometriosis without MSH2 and MSH6 expression. In Case 2, all endometriotic cells contiguous with carcinoma in the lumen of the ovarian cyst showed loss of the expression of MSH2 and MSH6. CONCLUSION: Ovarian endometriosis with MMR protein deficiency may progress to endometriosis-associated ovarian cancer in women with LS. Diagnosing endometriosis in women with LS during surveillance is important.

Curcumin-resveratrol nano-formulation counteracting hyperammonemia in rats.

Malnutrition and low dietary protein intake could be risk factors for developing peripheral and central hyperammonemia, especially in pediatrics. Both curcumin and resveratrol proved to be effective against several hepatic and cerebral injuries. They were reported to be beneficial in lowering circulating ammonia levels, yet both are known for their low bioavailability. The use of pharmaceutical nano-formulations as delivery systems for these two nutraceuticals could solve the aforementioned problem. Hence, the present study aimed to investigate the valuable outcome of using a combination of curcumin and resveratrol in a nanoemulsion formulation, to counteract protein-deficient diet (PDD)-induced hyperammonemia and the consequent complications in male albino rats. Results revealed that using a nanoemulsion containing both curcumin and resveratrol at a dose of (5 + 5 mg/kg) effectively reduced hepatic and brain ammonia levels, serum ALT and AST levels, hepatic and brain nitric oxide levels, oxidative DNA damage as well as disrupted cellular energy performance. In addition, there was a substantial increase in brain levels of monoamines, and a decrease in glutamate content. Therefore, it can be concluded that the use of combined curcumin and resveratrol nanoemulsion is an effective means of ameliorating the hepatic and cerebral adverse effects resulting from PDD-induced hyperammonemia in rats.

Neonatal D-bifunctional protein deficiency: a report of two cases and literature review / 中华围产医学杂志

Objective:To summarize the clinical characteristics and genetic etiology of infants with D-bifunctional protein deficiency (DBPD).Methods:This study involved two DBPD newborns who were hospitalized in the Second Affiliated Hospital of Wenzhou Medical University in August 2020 and November 2020. Clinical data including manifestations, radiographic findings and genetic testing results were retrospectively analyzed. Relevant articles up to November 2022 were retrieved from various databases including CNKI, Wanfang, CQVIP, Online Mendelian Inheritance in Man and PubMed using the terms of "D-bifunctional protein deficiency" and " HSD17B4" in both Chinese and English. Clinical data of the cases diagnosed with DBPD by genetic testing within two years of age were collected. Clinical features and genetic etiology of the children with DBPD were summarized by descriptive statistical analysis. Results:Both neonates in this report presented with dyspnea, hypotonia, intractable epilepsy, poor response, absence of primitive reflexes, and craniofacial malformation. Whole-exome sequencing revealed that patient 1 carried heterozygous variations of c.972+1G>T and c.727T>A (p.W243R) in the HSD17B4 gene, which were inherited from his father and mother, respectively. A homozygous variation of c.1333+4A>G in the HSD17B4 gene was identified in patient 2. All these mutations were pathogenic. Thirteen papers (12 in English and one in Chinese) involving 19 patients from 16 pedigrees were retrieved. Altogether 21 patients (eight males and 13 females) were included, and among them, four from two pedigrees were born to consanguineous parents. There were 21 patients with hypotonia, 20 with epileptic seizures (17 presenting with epileptic seizures within 5 d after birth) and 12 with craniofacial deformities including high forehead, long philtrum and high palatine arches. Genetic tests showed that 13 patients carried compound heterozygous variations in the HSD17B4 gene and eight patients had homozygous variations. Twenty-six variations in the HSD17B4 gene were detected, including 16 missense mutations, seven splicing mutations, two nonsense mutations and one frameshift mutation. Conclusion:DBPD should be considered and genetic tests should be given when newborns have dystonia and intractable epilepsy complicated by appearance deformity.

Self-Amplifying RNA Approach for Protein Replacement Therapy.

Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms.

Screening of Lynch syndrome in endometrial cancer in Iranian population with mismatch repair protein by immunohistochemistry.

Background: Lynch syndrome (LS) is one of the commonest genetic cancer syndromes, with an incidence rate of 1 per 250-1000 population. The aim of this study was to evaluate the frequency and characteristics of MMR deficiency in endometrial cancer in Iranian women. Methods: One hundred endometrial carcinoma cases who referred to the gynecological oncology clinic of Imam Hossein Medical Center located in Tehran, Iran, from 2018 to 2020 were included in the study. Immunohistochemistry (IHC) evaluation was performed mainly on the hysterectomy specimens of all endometrial cancer (EC) patients to assess MMR proteins (MLH1, MSH2, MSH6, and PMS2) expression. Results: A total of 23 out of 100 (23%) cases were identified through IHC screening to be MMR-deficient. The most common types were loss of MLH1/PMS2 (17.4%) and solitary MSH2 (17.4%) expressions followed by PMS2/MSH2 loss (13%). MMR deficiency (dMMR) histopathology was significantly overrepresented in patients with family history of cancer or Lynch syndrome (LS) associated cancers (p-values of 0.016 and 0.005, respectively). The rate of myometrial invasion and lower uterine segment involvement were also significantly higher in dMMR EC patients compared to MMR-intact EC (p-value of 0.021 and 0.018, respectively). Conclusion: MMR deficiency, observed in 23% of endometrial cancer cases, was associated with higher rates of poor prognostic factors including myometrial invasion and lower uterine segment involvement. The presence of positive family history of cancer and family history of LS-associated cancer increased the probability of MMR-deficiency in endometrioid endometrial cancer to 47% and 70%, respectively.

Variable Expression of Lung Disease Due to a Novel Homozygous ABCA3 Variant.

Background: Mutations in the ATP-binding cassette transporter A3 (ABCA3) gene are one of the most common surfactant disorders leading to interstitial lung diseases (ILD). The clinical spectrum and severity of lung disease caused by ABCA3 deficiency due to missense variants is variable. Case Presentations: A novel ABCA3 c.3135G>C (p.Gln1045His) mutation was identified at the homozygous state in 3 subjects from 2 unrelated families: one 19-month-old boy with severe ILD and his homozygous pauci-symptomatic mother, and one 10-year-old girl with moderate late-onset ILD. Corticosteroid pulses associated with hydroxychloroquine were beneficial for both children. Conclusion: We illustrate here the huge intra- and interfamilial phenotypic variability associated with the same homozygous missense ABCA3 mutation, and the benefit of identifying the disease for treatment, follow-up, and appropriate genetic counseling.

Influence of protein intake on the changes in skeletal muscle mass after kidney transplantation.

BACKGROUND & AIMS: Skeletal muscle mass decreases in patients with chronic kidney disease, especially those on dialysis with end-stage kidney disease. On the other hand, the recovery of renal function due to successful kidney transplantation (KT) improves skeletal muscle mass loss. However, low protein intake may influence the changes in skeletal muscle mass after KT. The aim of the present study is to examine the association of the changes in skeletal muscle mass with protein intake in kidney transplant recipients (KTRs). METHODS: A cohort study was conducted in KTRs and living-kidney donors (LKDs). Skeletal muscle mass index (SMI) was measured using bioelectrical impedance analysis before KT and at 1 month and 12 months after KT. Protein intake was calculated with 24-h urine urea nitrogen from the Maroni formula at 12 months after KT. To evaluate the association between protein intake and the changes in SMI during the first year after KT, we performed a multivariable regression analysis adjusted for covariates including age, sex, cumulative glucocorticoids, cumulative hospitalization, diabetes mellitus, and SMI before KT. RESULTS: In KTRs (n = 64), the median SMI was 7.26 kg/m2 before KT, which decreased to 7.01 kg/m2 at 1 month after KT and increased to 7.55 kg/m2 at 12 months after KT. In LKDs (n = 17), the median SMI was 6.24 kg/m2 before KT which increased to 6.40 kg/m2 at 1 month after KT and further increased to 6.95 kg/m2 at 12 months after KT. The changes in SMI during the 1-year period after KT exhibited a positive correlation with protein intake (p = 0.015) after adjustment. The predicted value of protein intake in KTRs, whose values of SMI before KT and at 12 months after KT were the same, was 0.72 g/kg ideal body weight (IBW)/day using the multivariable non-linear regression model. CONCLUSIONS: In KTRs, insufficient protein intake adversely affected the recovery from skeletal muscle mass loss after KT. Therefore, a protein intake of at least more than 0.72 g/kg IBW/day, the predicted value obtained in the present study, might be recommended for KTRs suffering from skeletal muscle mass loss.

Emerging sources and applications of alternative proteins: An introduction.

Food protein is an essential macronutrient. Even though daily per capita supply of protein has increased globally from 61g in 1961 to 81g in 2013, and most people in the developed world have sufficient protein intake from their diets, however, protein deficiencies continue to be pervasive globally. Protein deficiency is the single major factor responsible for impaired growth and suboptimal health worldwide. Animal proteins are high quality and contain adequate and balanced amino acids, animal protein production however is inefficient and resource intensive. Alternative proteins are expected to provide the solution to meet the growing protein demand within the environmental limits. Alternative proteins include proteins from plants (i.e., grains, legumes, pulse, and nuts), fungus (i.e., mushrooms), algae, insects and cultured (lab-grown) meat that can be used to replace conventional animal proteins. Major concerns for human consumption of alternative proteins are inferior organoleptic properties, consumer acceptability, affordability, and sustainability. There is a need to develop culturally diversified alternative proteins to mitigate global protein malnutrition. Food proteins are also found applications in biomaterials and as a source of bioactive peptides.

Limited Supply of Protein and Lysine Is Prevalent among the Poorest Households in Malawi and Exacerbated by Low Protein Quality.

We estimated dietary supplies of total and available protein and indispensable amino acids (IAAs) and predicted the risk of deficiency in Malawi using Household Consumption and Expenditure Survey data. More than half of dietary protein was derived from cereal crops, while animal products provided only 11%. The supply of IAAs followed similar patterns to that of total proteins. In general, median protein and IAA supplies were reduced by approximately 17% after accounting for digestibility, with higher losses evident among the poorest households. At population level, 20% of households were at risk of protein deficiency due to inadequate available protein supplies. Of concern was lysine supply, which was inadequate for 33% of households at the population level and for the majority of the poorest households. The adoption of quality protein maize (QPM) has the potential to reduce the risk of protein and lysine deficiency in the most vulnerable households by up to 12% and 21%, respectively.

Reversible sensory neuropathy in mitochondrial trifunctional protein deficiency.

Axonal peripheral neuropathy is a common complication of mitochondrial trifunctional protein (MTP) deficiency and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency that is usually considered progressive. Current treatment strategies are not able to fully prevent neuropathic symptoms in the majority of patients. We herein report three sisters with genetically proven MTP deficiency who were untreated until adolescence, when electrophysiological studies first revealed isolated axonal sensory neuropathy. Apart from mild exercise intolerance and missing deep tendon reflexes of the lower extremities, all three girls were clinically asymptomatic. A fat-reduced and fat-modified diet together with a reduction of the nocturnal fasting time resulted in complete normalisation of the electrophysiological studies after 1 year of dietary treatment. Our findings suggest that neuropathy might be responsive to dietary interventions in MTP patients at a very early stage of disease.

Thermo-sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy.

Mitochondrial trifunctional protein (MTP) is involved in long-chain fatty acid ß-oxidation (lcFAO). Deficiency of one or more of the enzyme activities as catalyzed by MTP causes generalized MTP deficiency (MTPD), long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), or long-chain ketoacyl-CoA thiolase deficiency (LCKATD). When genetic variants result in thermo-sensitive enzymes, increased body temperature (e.g. fever) can reduce enzyme activity and be a risk factor for clinical decompensation. This is the first description of five patients with a thermo-sensitive MTP deficiency. Clinical and genetic information was obtained from clinical files. Measurement of LCHAD and LCKAT activities, lcFAO-flux studies and palmitate loading tests were performed in skin fibroblasts cultured at 37°C and 40°C. In all patients (four MTPD, one LCKATD), disease manifested during childhood (manifestation age: 2-10 years) with myopathic symptoms triggered by fever or exercise. In four patients, signs of retinopathy or neuropathy were present. Plasma long-chain acylcarnitines were normal or slightly increased. HADHB variants were identified (at age: 6-18 years) by whole exome sequencing or gene panel analyses. At 37°C, LCHAD and LCKAT activities were mildly impaired and lcFAO-fluxes were normal. Remarkably, enzyme activities and lcFAO-fluxes were markedly diminished at 40°C. Preventive (dietary) measures improved symptoms for most. In conclusion, all patients with thermo-sensitive MTP deficiency had a long diagnostic trajectory and both genetic and enzymatic testing were required for diagnosis. The frequent absence of characteristic acylcarnitine abnormalities poses a risk for a diagnostic delay. Given the positive treatment effects, upfront genetic screening may be beneficial to enhance early recognition.

Intergenerational protein deficiency and adolescent reproductive function of subsequent female generations (F1 and F2) in rat model.

BACKGROUND: Efficient reproductive function is an important characteristic that has evolved through natural selection. Nutrition can modulate reproductive activities at different levels, and its effect on reproduction is deemed complex and less predictable. OBJECTIVE: This study aims at investigating the underlying effect of persistent dietary protein deficiency during early life on reproductive parameters of subsequent (F1 and F2) generations. METHOD: Rats in group of four (4) were fed daily, different ration of protein diet (PD) formulated as: 21% protein diet, 10%protein diet, 5%protein diet and control diet (rat chow, containing 16-18% protein). They were fed ad libitum before mating, throughout gestation and lactation, and next generations were weaned to the maternal diet. Reproductive function analysis (which include; gestation and pubertal hormonal profiling, onset of puberty, oestrus cyclicity, sexual response) and morphometric analysis of the ovarian structure were carried out to assess associated consequences. RESULTS: There was significant reduction in the fertility index (Control; 85.8%., 21%PD; 88.43%., as compared to 10%PD; 65.9%., 5%PD; 35.78%.,) at F1, also recurring in F2 respectively as a consequence of altered reproductive function in the protein deficient models at P ≤ 0.05. Low protein diet posed suboptimal intrauterine condition, which was linked to increased prenatal morbidity and mortality (control; 11.3%., 21%PD; 3.3%., 10%PD; 27.4%., 5%PD; 32.9%), low birthweight (control; 5.29, 4.9 g., 21%PD; 5.5, 5.06 g., 10%PD; 4.05, 3.86 g., 5%PD; 2.7, 2.5 g) at F1 and F2 respectively, delayed onset of puberty (with average pubertal age set at: control; PND 36, 21%PD; PND 38 while 10%PD; PND 62., and 5%PD; PND 67), followed by induced cycle irregularity, altered follicular maturation and endocrine dysfunction, more severe in 5%PD. CONCLUSION: Reproductive status of a female organism depends on the maintenance of ovarian structure and function that has been associated with the hypothalamic pituitary-gonadal axis, hormonal events and sexual maturity. There is therefore an association between persistent early life protein deficiency and reproductive response which mechanistically involves life-long changes in key ovarian cytoarchitecture and function.