Comparing students' performance in self-directed and directed self-learning in College of Medicine, University of Bisha.

Background: Student-centered learning strategy increases the likelihood of graduation of competent, self-dependent, and problem-solving physicians. The University of Bisha, College of Medicine (UBCOM) adopted self-directed learning (SDL) represented by problem-based learning (PBL), and directed self-learning (DSL) represented by team-based learning (TBL). Aim: To compare the students' performance in SDL and DSL among UBCOM students. Methodology: A total of 502 multiple choice questions (MCQs) from the mid-course and final exams were collected by the relevant subject experts from nine courses during the period from September 2020 till June 2023 that adopted PBL and TBL; 247 MCQs related to PBL and 255 related to TBL. Psychometric analysis was used to determine difficult, easy, and optimum questions (≤25%, ≥90%, and 26-89%, respectively). Point biserial as <0.19, 0.20-0.29, 0.30-0.39, and >0.40 which indicate poor, marginal, good, and excellent point biserial, respectively. Finally, the number of functional distractors was attempted by >5% of the candidates. Results: No significant differences were noted for the students' performance in MCQs related to PBL (representing self-directed, small group learning tool), and TBL (representing directed-self, large group learning tool) regarding difficulty index (DI), point biserial, and distractors functionality. Conclusion: It has been observed that there is no difference in students' performance whether PBL or TBL is used for learning Basic Medical Science courses. Small group learning such as PBL needs more resources in comparison to large group learning as in TBL, therefore any institute can decide on the adopted learning strategy depending on its resources and the number of students.

Linagliptin, a DPP-4 inhibitor, activates AMPK/FOXO3a and suppresses NFκB to mitigate the debilitating effects of diethylnitrosamine exposure in rat liver: Novel mechanistic insights.

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.

STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TßRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations.

Liver fibrosis is a progressive condition characterized by the build-up of fibrous tissue resulting from long-term liver injury. Although there have been advancements in research and treatment, there is still a need for effective antifibrotic medication. HSP90 plays a crucial role in the development of fibrosis. It acts as a molecular chaperone that assists in the proper folding and stability of TßRII, potentially regulating the signaling of TGF-ß1. It has been established that TßRII can be degraded through the proteasome degradation system, either via ubiquitination-dependent or -independent pathways. In the present study, STA9090 demonstrated promising effects in both in vitro and in vivo models. It reduced LDH leakage, prolonged the survival rate of hepatocytes in rats with liver fibrosis, and improved liver function. Importantly, STA9090 exerted pleiotropic effects by targeting proteins involved in limiting collagen production, which resulted in improved microscopic features of the rat livers. Our findings suggest that STA9090-induced inhibition of HSP90 leads to the degradation of TßRII, a fibrogenic client protein of HSP90, through the activation of the 20S proteasomal degradation system. We also revealed that this degradation mechanism is not dependent on the autophagy-lysosomal pathway. Additionally, STA9090 was found to destabilize HIF-1α and facilitate its degradation, leading to the reduced transcription of VEGF. Moreover, STA9090's ability to deactivate the NFκB signaling pathway highlights its potential as an anti-inflammatory and antifibrotic agent. However, further research is necessary to fully elucidate the underlying mechanisms and fully capitalize on the therapeutic benefits of targeting HSP90 and associated pathways.

Response of Diverse Peanut Cultivars to Nano and Conventional Calcium Forms under Alkaline Sandy Soil.

Calcium is one of the most limiting factors for the growth and reproduction of peanut, which ultimately affects pod and seed yields. A two-year field experiment was carried out to assess the impact of five calcium applications, including nano-calcium and conventional forms, on growth, leaf nutrient content, yield traits, and quality parameters of three diverse peanut cultivars (Ismailia-1, Giza-5, and Giza-6). The applied calcium applications were calcium sulfate, which is recommended for commercial peanut cultivation and commonly referred to as gypsum (coded as Ca-1), calcium nitrate (Ca-2), nano-calcium nitrate (Ca-3), 50% calcium nitrate + 50% nano-calcium (Ca-4), and 50% calcium sulfate + 50% nano-calcium (Ca-5). Calcium sulfate (gypsum, Ca-1) was soil-supplied during the seedbed preparation as recommended, while the other calcium applications (Ca-2, Ca-3, Ca-4, and Ca-5) were exogenously sprayed three times at 30, 45, and 60 days after sowing. The soil of the experimental site was alkaline, with a high pH of 8.6. The results revealed significant differences among cultivars, calcium applications, and their interactions. The soil-supplied gypsum Ca-1 displayed lower agronomic performance on all recorded growth, leaf nutrient content, yield traits, and quality parameters. On the other hand, the foliar-supplied calcium, particularly Ca-4 and Ca-5, displayed superior effects compared to the other simple calcium forms. Ca-4 and Ca-5 produced significantly higher seed yield (3.58 and 3.38 t/ha) than the simple recommended form (Ca-1, 2.34 t/ha). This could be due to the difficulty of calcium uptake from soil-supplied calcium under high soil pH compared to the exogenously sprayed nano-calcium form. Moreover, the superior performance of Ca-4 and Ca-5 could be caused by the mixture of fertilizers from the synergistic effect of calcium and nitrate or sulfate. Furthermore, the effect of nitrate was applied in nano form in the Ca4 and Ca-5 treatments, which contributed to improving nutrient uptake efficiency and plant growth compared to the other treatments. The peanut cultivar Giza-6 showed superiority for most measured traits over the other two cultivars. The interaction effect between the assessed cultivars and calcium applications was significant for various traits. The cultivar Giza-6 showed a significant advantage for most measured traits with the mixture of 50% calcium nitrate + 50% nano-calcium (Ca-4). Conclusively, the results pointed out the advantage of the exogenously sprayed nano-calcium form combined with calcium nitrate or calcium sulfate for promoting growth, leaf nutrient content, yield, and quality traits of peanut, particularly with high-yielding cultivars under sandy soil with high pH.

Improving the Tolerance to Salinity Stress in Lettuce Plants (Lactuca sativa L.) Using Exogenous Application of Salicylic Acid, Yeast, and Zeolite.

Salinity is among the most limiting factors of crop production worldwide. This study aims to investigate the influence of the exogenous application of zeolite, yeast, and salicylic acid in alleviating the negative effect of salt stress under field conditions. Lettuce plants (Lactuca sativa L. cv. Batavia) were tested in a split-plot arrangement replicated three times. The salt stress was applied as a whole-plot factor in the concentrations (0 mM, 50 mM, 100 mM, and 150 mM NaCl). After 28 days of sowing, the plants were sprayed twice during the foliage growth with (control, salicylic acid 0.02%, yeast extract 3%, and zeolite 0.5%) as a split-plot factor. The length of roots and shoots, the number and area of leaves, and the biomass accumulation (dry and fresh weights) were measured 50 days after sowing. The concentrations of total soluble sugars, proline, Chlorophylls a and b in leaves have also been quantified. Salt stress significantly reduced the growth and the total chlorophyll of the lettuce plants (p < 0.05) and increased their proline and sugar contents'. Zeolite application improved the growth of lettuce at 0 and 50 mM NaCl, but at the highest salinity level only the number of leaves was improved by 15%. At a mild salinity stress, the application of salicylic acid has significantly (p < 0.05) increased the root length, height of plant, chlorophyll, and proline contents. Regarding the high stress levels (100 and 150 mM NaCl), yeast application showed the best tolerance to salinity stress by improving significantly most of the growth parameters (p < 0.05) but with lower proline, sugar, and chlorophyll contents. In general, foliar spray of yeast extract may offer a good alternative source of nutrients through leaves, leading to a better tolerance of the high salt stress exerted on roots.

Effects of Plant-Growth-Promoting Rhizobacteria (PGPR) and Cyanobacteria on Botanical Characteristics of Tomato (Solanum lycopersicon L.) Plants.

Tomatoes are an important agricultural product because they contain high concentrations of bioactive substances, such as folate, ascorbate, polyphenols, and carotenoids, as well as many other essential elements. As a result, tomatoes are thought to be extremely beneficial to human health. Chemical fertilizers and insecticides are routinely utilized to maximize tomato production. In this context, microbial inoculations, particularly those containing PGPR, may be utilized in place of chemical fertilizers and pesticides. In this study, we investigated the effects of PGPR (Bacillus subtilis, and Bacillus amyloliquefaciens) and cyanobacteria when utilized alone, and in conjunction with each other, on the growth, quality, and yield of fresh fruits of tomato plants. The results showed that the inoculation significantly increased all measured parameters of tomato plants compared with the control. Combined use of B. subtilis and B. amyloliquefaciens had a positive impact on tomato yield, increasing fruit yield. Moreover, leaflet anatomical characteristics were altered, with increased thickness of the upper epidermis, lower epidermis, palisade tissue, spongy tissue, and vascular bundles. Tomato fruit quality was improved, as measured by an increased number of fruit per plant (76% increase), fruit weight (g; 33% increase), fruit height (cm; 50% increase), fruit diameter (cm; 50%), total soluble solids (TSS; 26% increase), and ascorbic acid (mg/100 g F.W.; 75% increase), relative to the control, in the first season. In addition, fruit chemical contents (N, P, and K) were increased with inoculation. The results suggest that inoculation with B. subtilis and B. amyloliquefaciens could be successfully used to enhance tomato plant growth and yield.

Dermatology Life Quality Index in Patients with Dermatophytosis in a Tertiary Care Centre of Bangladesh.

In our country a huge number of populations are suffering from dermatophytosis. During the last few years, the number of patients affected by dermatophytosis has been increasing. Dermatophytosis tends to be prolonged, recurrent and persistent course which can affect quality of life (QoL). The aim of this study was to seek out the effect of dermatophytosis on the quality of life of the patients of dermatophytosis and to analyze its relationship with various demographic and clinical factors. This was a cross-sectional study in which 306 patients aged ≥16 years with dermatophytosis were included and evaluated for impact of dermatophytosis on quality of life using dermatology life quality index (DLQI) questionnaire. Independent sample t-test and one way ANOVA were used to find out statistical associations between various variables and mean DLQI scores, wherever applicable. The mean DLQI score in this study was 13.07±8.51. Majority (39.5%) subjects had a 'very large' effect on the QoL. Mean DLQI was significantly higher in young subjects, patients with longer duration of disease, more body surface area involved, involvement of more than one sites (generalized involvement) and topical steroid containing preparation users (p<0.05). This study revealed that the quality of life is adversely affected by dermatophytosis. Hence, Steps must be taken for proper counseling and management, along with early detection and elimination of topical steroid use in dermatophytosis.

Mosaic dysfunction of mitophagy in mitochondrial muscle disease.

Mitophagy is a quality control mechanism that eliminates damaged mitochondria, yet its significance in mammalian pathophysiology and aging has remained unclear. Here, we report that mitophagy contributes to mitochondrial dysfunction in skeletal muscle of aged mice and human patients. The early disease stage is characterized by muscle fibers with central nuclei, with enhanced mitophagy around these nuclei. However, progressive mitochondrial dysfunction halts mitophagy and disrupts lysosomal homeostasis. Interestingly, activated or halted mitophagy occur in a mosaic manner even in adjacent muscle fibers, indicating cell-autonomous regulation. Rapamycin restores mitochondrial turnover, indicating mTOR-dependence of mitochondrial recycling in advanced disease stage. Our evidence suggests that (1) mitophagy is a hallmark of age-related mitochondrial pathology in mammalian muscle, (2) mosaic halting of mitophagy is a mechanism explaining mosaic respiratory chain deficiency and accumulation of pathogenic mtDNA variants in adult-onset mitochondrial diseases and normal aging, and (3) augmenting mitophagy is a promising therapeutic approach for muscle mitochondrial dysfunction.

Post-abortion care services at Red Sea State - Sudan.

BACKGROUND: Although there are safe and effective methods of abortion, unsafe abortions still widely spread, mainly in underdeveloped countries. OBJECTIVE: Study of post abortion care services at Red Sea State to address rate and utilization of post-abortion care package. METHODS: This is a descriptive (observational hospital-based study), conducted at Port Sudan Maternity hospital (May 2018-May 2019). The sample included all patients with inevitable and incomplete miscarriage. RESULTS: The total admissions to emergency in gynaecological department during the study period was 9525 cases, of them 1077 cases of abortion, hence the rate was 11.3%. Spontaneous onset occurred in 631 (58.6%) and induced in 446 (41.4%). Surprisingly very few surgical evacuations done in 2 (0.2%). 710 (66.1%) evacuated by Misoprostol and MVA done for 362 (33.7%). Patients who received family planning and counseling were 223 (20.7%). CONCLUSION: in conclusion the rate of abortion was 11.3%, high incidence of induced abortion and high non-surgical evacuation. Utilization of care package is reasonable.

Risk factors of placenta previa with maternal and neonatal outcome at Dongola/Sudan.

BACKGROUND: Placenta previa is a major cause of hemorrhage affecting 0.4-0.5% of all pregnancy's early detection of cases and senior input will significantly reduce maternal and fetal morbidity and mortality. OBJECTIVES: The aim of the study is to determine risk factors, fetal and maternal outcome in pregnancy complicated by placenta previa. METHOD: This is descriptive cross-sectional study in women diagnosed with placenta previa at Dongola maternity hospital, Sudan from December 2018 to June 2019. RESULTS: There were 3,674 deliveries and 52 cases of placenta previa during the study period with prevalence of 1.4%. The average age of the patients was 34.8 years and most of them were above 35 years (53.8%), and (63.5%) were para 3 and more. Other identified risk factors included previous cesarean section (69.1%), previous uterine evacuation (13.5%), and assisted reproductive technique (5.8%). Maternal complications were hemorrhage needing blood transfusion (40.4%), cesarean hysterectomy (21.2%), and bladder injury (3.8%), but (34.6%) were with good outcome and no maternal death. NICU admission with RDS (25%), prematurity (25%), and death (5.8%) were the fetal complications, while in (44.2%) fetal outcome was good. CONCLUSION: The most identifiable risk factors for placenta previa were previous uterine scars, advanced maternal age, and multiparity. And it is associated with adverse maternal and fetal outcomes.

Detection of peste des petits ruminants virus in pneumonic lungs from clinically apparently healthy camels slaughtered at Tambul slaughterhouse, Central Sudan.

The study investigated the presence and prevalence of peste des petits ruminants (PPR) viral antigens among camels in Tambul area, Gezira State, Central Sudan, regardless of its sex, age and breed, and their possible contribution in the epidemiology of the disease in the Sudan. Hundred pneumonic lung tissues were aseptically collected from clinically apparently healthy camels showed no signs of illness at ante-mortem examination, from Tambul slaughterhouse, Tambul area, Gezira State, Central Sudan, between November and December 2018. Samples were collected based on presence of the pneumonic signs, at the tissue level, including congestion of the lungs, presence of abscesses, fragility, changes in colour and thickness of the tissue. In order to detect PPR viral antigen, haemagglutination (HA) test was employed on lung tissue homogenate, using chicken RBCs suspension, which gave a positive reaction in 17-19 min. PPRV antigen was detected in 98 of camel samples with an overall antigenic prevalence of 98%. Of note, the HA titres achievable ranged from 4 to 256 HA units (HAU) with mean titre of 14.4 HAU, whereas apparently most of the samples achieved HA titres of 8 HAU. The results demonstrated presence of PPR viral antigens associated with pneumonia in camels indicating exposure of these camels to PPRV and probably presence of subclinical infection. Infection of species other than small ruminants suggests the fact that camels are potential hosts for PPRV and might play a role (or not) in the epidemiology of the disease. Further studies are needed to demonstrate if camels are able to transmit PPRV for in-contact small ruminants or other animal species.

Effect of Salt Stress and Foliar Application of Salicylic Acid on Morphological, Biochemical, Anatomical, and Productivity Characteristics of Cowpea (Vigna unguiculata L.) Plants.

The present study aimed to investigate the impact of salinity on vegetative growth, chemical constituents, and yields of cowpeas (Vigna unguiculata) and the possible benefits of salicylic acid (SA) on these plants after damage from salinity. To achieve these objectives, two pot experiments were carried out at the Faculty of Agriculture, Al-Azhar University, Egypt, during the two growing seasons of 2019 and 2020. The results revealed that salinity significantly decreased, and SA treatment substantially increased the plant height, number of compound leaves, number of internodes per plant, fresh weights of leaves and stems, productivity, photosynthetic pigments content, and concentrations of nitrogen (N), phosphorus (P), and potassium (K) of the cowpea plants compared with the control. The anatomical structure of stems and leaves of the plants were also investigated, and it was found that positive variations in the anatomical structure of the median portion of the main stems and blades of mature foliage leaves were detected in the stressed and SA-treated plants. In conclusion, SA treatment increased the salt stress tolerance of cowpea plants by improving the morphological and physiological attributes of the plants.

Detection of peste des petits ruminants virus in pneumonic lungs from apparently healthy sheep and goats slaughtered at Al-Hasaheisa slaughterhouse, Gezira state, central Sudan.

The study aimed to investigate the presence of peste des petits ruminants (PPR) in pneumonic lung tissues from clinically apparently healthy sheep and goats and further demonstrating its prevalence in Gezira state, central Sudan. During March 2019, 99 pneumonic lung samples were collected from apparently healthy sheep (80) and goats (19) from Al-Hasaheisa slaughterhouse located in Al-Hasaheisa locality, Gezira state. Using the haemagglutination (HA) test for the detection of peste des petits ruminants virus (PPRV) antigen, an overall antigenic prevalence of 86.9% was demonstrated in sheep and goats lung tissue homogenate. Of note, the prevalence of PPRV is higher in goats (100%) compared to sheep (83.7%). In this study, the reported increasing prevalence of PPR in central Sudan might be because of insufficient vaccination of animals. The findings of the present study indicated the widespread of PPR amongst sheep and goats in Al-Hasaheisa, Gezira state. Detection of PPRV antigen in the pneumonic lung samples is an indication of exposure of these animals to PPRV or presence of PPR viral infection and demonstrates the role of PPR as the cause of pneumonia in small ruminants. In fact, the circulation of the virus in clinically apparently healthy animals poses a threat for other in-contact susceptible animals and could play a significant role in the spread of the disease.

Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy.

NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.govNCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.

Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA Deletions.

Mitochondrial dysfunction elicits stress responses that safeguard cellular homeostasis against metabolic insults. Mitochondrial integrated stress response (ISRmt) is a major response to mitochondrial (mt)DNA expression stress (mtDNA maintenance, translation defects), but the knowledge of dynamics or interdependence of components is lacking. We report that in mitochondrial myopathy, ISRmt progresses in temporal stages and development from early to chronic and is regulated by autocrine and endocrine effects of FGF21, a metabolic hormone with pleiotropic effects. Initial disease signs induce transcriptional ISRmt (ATF5, mitochondrial one-carbon cycle, FGF21, and GDF15). The local progression to 2nd metabolic ISRmt stage (ATF3, ATF4, glucose uptake, serine biosynthesis, and transsulfuration) is FGF21 dependent. Mitochondrial unfolded protein response marks the 3rd ISRmt stage of failing tissue. Systemically, FGF21 drives weight loss and glucose preference, and modifies metabolism and respiratory chain deficiency in a specific hippocampal brain region. Our evidence indicates that FGF21 is a local and systemic messenger of mtDNA stress in mice and humans with mitochondrial disease.

Nodular Mucinosis of Male Breast: A Rare Case Report.

Multinodular accumulation of stromal mucin in breast known as nodular mucinosis is an extremely rare condition of breast. Alternatively it is known as myxoma or nerve sheath myxoma of breast. This benign lesion is confined to only nipple and areola region presenting as slow growing, soft and non tender lobulated mass. Histopathologically it reveals well circumscribed non-encapsulated myxoid/mucinous lesion with few infiltration of spindle cells within a collaginized stroma. The mucinous substance is stained positively with Alcian blue. Mucinous carcinoma or phylloids tumour are important differential diagnosis of nodular mucinosis of breast. Here we report a case of nodular mucinosis of male breast with clinical, radiological and pathological findings with differential diagnosis and treatment modalities.

Phenotypic effects of dietary stress in combination with a respiratory chain bypass in mice.

The alternative oxidase (AOX) from Ciona intestinalis was previously shown to be expressible in mice and to cause no physiological disturbance under unstressed conditions. Because AOX is known to become activated under some metabolic stress conditions, resulting in altered energy balance, we studied its effects in mice subjected to dietary stress. Wild-type mice (Mus musculus, strain C57BL/6JOlaHsd) fed a high-fat or ketogenic (high-fat, low-carbohydrate) diet show weight gain with increased fat mass, as well as loss of performance, compared with chow-fed animals. Unexpectedly, AOX-expressing mice fed on these metabolically stressful, fat-rich diets showed almost indistinguishable patterns of weight gain and altered body composition as control animals. Cardiac performance was impaired to a similar extent by ketogenic diet in AOX mice as in nontransgenic littermates. AOX and control animals fed on ketogenic diet both showed wide variance in weight gain. Analysis of the gut microbiome in stool revealed a strong correlation with diet, rather than with genotype. The microbiome of the most and least obese outliers reared on the ketogenic diet showed no consistent trends compared with animals of normal body weight. We conclude that AOX expression in mice does not modify physiological responses to extreme diets.

Heavy metals accumulation from sewage sludge in the Nile tilapia Oreochromis niloticus (Trewavas, 1983) during a sludge-earthworm-fish short-term cycling.

Municipal sewage sludge from waste-water treatment is an important nutritional source for sustainable agriculture. Here, we report on the assessment of the accumulation of heavy metals in Nile tilapia Oreochromis niloticus (Trewavas 1983) fed on earthworms Eisenia fetida reared on soil treated with different concentrations of sewage sludge (25% and 100%) during sludge-earthworm-fish short-term cycling. In this short-term cycling the Nile tilapia collected from the White Nile were chosen as final consumers, whereas the earthworms reared on loam soil mixed with different ratios of sludge were used as a feed for the final consumers. Our results indicate that the concentrations of Cd2+, Cr2+, Pb2+ and Zn2+ in the sludge treated soil are proportional to the sludge content in the soil. Importantly, the accumulation of these heavy metals was significantly low in the earthworms and the Nile tilapia in comparison with the treated soil and that these concentrations in the Nile tilapia were below the international limits recommended by the US Environmental Protection Agency (2014). Moreover, the growth and overall flesh quality of the fish were improved as indicated by the growth increase up to 146% when fed on earthworm reared in 100% sludge. Additionally, our physico-chemical properties (i.e. pH, soil moisture, electric conductivity and organic matters) evaluation on the soil indicates an improvement of the soil quality when mixed with sewage sludge. These results suggest a sustainable application of sewage sludge in fish culture owing to its high nutritional values, low cost, and low risk of hazardous heavy metals when using primary consumers with heavy metals bioaccumulation capability such as E. fetida.

mTORC1 Regulates Mitochondrial Integrated Stress Response and Mitochondrial Myopathy Progression.

Mitochondrial dysfunction elicits various stress responses in different model systems, but how these responses relate to each other and contribute to mitochondrial disease has remained unclear. Mitochondrial myopathy (MM) is the most common manifestation of adult-onset mitochondrial disease and shows a multifaceted tissue-specific stress response: (1) transcriptional response, including metabolic cytokines FGF21 and GDF15; (2) remodeling of one-carbon metabolism; and (3) mitochondrial unfolded protein response. We show that these processes are part of one integrated mitochondrial stress response (ISRmt), which is controlled by mTORC1 in muscle. mTORC1 inhibition by rapamycin downregulated all components of ISRmt, improved all MM hallmarks, and reversed the progression of even late-stage MM, without inducing mitochondrial biogenesis. Our evidence suggests that (1) chronic upregulation of anabolic pathways contributes to MM progression, (2) long-term induction of ISRmt is not protective for muscle, and (3) rapamycin treatment trials should be considered for adult-type MM with raised FGF21.