Outcome of pediatric living donor liver transplant: Experience from Pakistan; a resource limited setting.

INTRODUCTION: Liver transplantation (LT) has emerged as a lifesaving modality for many liver diseases in children. Pediatric LT is an established treatment in the Western world but is relatively a new procedure in resource-limited countries like Pakistan. The study aims to highlight the outcomes and survival of pediatric recipients from the first pediatric liver transplant center in Pakistan. METHOD: A retrospective analysis of pediatric LT was done from 2012 to 2019. The study was conducted in the Hepatobiliary and liver transplant department of Shifa International Hospital (SIH), Islamabad. A detailed analysis for indications for pediatric LT, survival, and complications was done. RESULTS: Forty-five patients under 18 years of age underwent Living donor liver transplant (LDLT) in SIH. Median age was 9 years and M:F of 2:1. Cryptogenic liver disease followed by Wilson disease were the two most common indications of LT. The majority of patients had chronic liver disease 34 (75%) while 11 (24%) had acute liver failure. The right lobe graft was the most common type of graft 19 (42.2%). Thirty days, 1-year, 3-year, and 5-year survival was 77.8%, 75.6%, 73.3%, and 60.6% respectively. Mortality was highest in patients with biliary atresia 4 (33%). Causes of death included pulmonary embolism, sepsis, surgical complications, and acute kidney injury. Mean survival was 88.850 months (±7.899) (CI 73.369-104.331). CONCLUSION: Pediatric LDLT has offered disease-free survival for patients. Survival can improve further with nutritional rehabilitation and anticipation and management of post-operative complications.

Estrogen receptor alpha (ESR1) gene polymorphism (rs2234693 and rs2046210) with breast cancer risk in pashtun population of Khyber Pakhtunkhwa.

BACKGROUND: Breast cancer susceptibility is greatly influenced by single nucleotide polymorphisms (SNPs) both in penetrance and non-penetrance genes. The Estrogen Receptor Alfa (ESR1- rs2234693 and rs2046210) have been reported as risk factor of breast cancer in different ethnic groups with inconsistent results. In this study the association of ESR1 (rs2234693 and rs2046210) with breast cancer risk was investigated in patients of Khyber Pakhtunkhwa. METHODS: A total of 312 females including 162 breast cancer patients and 150 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR. RESULTS: Our results revealed that ESR1-rs2234693 risk allele (C) (P = 0.21, OR = 1.27, CI = 0.87 to 1.87) and containing genotypes CC (P = 0.68, OR = 1.24, CI = 0.42 to 3.68) and TC (P = 0.23, OR = 1.32, CI = 0.83 to 2.13) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P < 0.0001, OR = 2.42, CI = 1.74 to 3.38) and corresponding genotypes GA (P = 0.0001, OR = 2.55, CI = 1.62 to 4.03) and AA (P = 0.02, OR = 2.20, CI = 1.12 to 4.34) were significantly associated with higher risk of breast cancer. Moreover, ESR1-rs2234693 was significantly (P < 0.05) associated with family history, stages, PR status, ER status and luminal B. The ESR1-rs2046210 showed significant (P ≤ 0.05) association with menstrual status, tumor grade and TNBC. Both the SNPs showed non-significant (P > 0.05) association with nulliparity, nodal status, HER2 status, metastasis, HER2 enriched subtype and luminal A. CONCLUSION: It is concluded that ESR1-rs2234693 is not associated with breast cancer, while rs2046210 is significantly associated with the risk of breast cancer in Khyber Pakhtunkhwa population. Further, to confirm the exact situation of ESR1 polymorphism, ESR1 existing and other SNPs need to be investigated in diverse data sets.

Biliary atresia-An experience from the first pediatric liver transplant center in Pakistan.

BACKGROUND: Biliary atresia (BA) is the most common cause of neonatal cholestatic syndrome. The true incidence of BA in Pakistan is largely unknown. AIM: This study aimed to report the clinical features, age at diagnosis and outcomes of biliary atresia from the first pediatric liver transplant center in Pakistan. METHODS: The study was done in Shifa International hospital from 2013 to 2020. All babies who had biliary atresia confirmed by laboratory investigation were included. Demographic data, age of presentation, clinical presentation, supporting investigations like liver function tests, ultrasound abdomen, HIDA scan and liver biopsy were noted. Outcome related to Kasai portoenterostomy, liver transplant, complications and immunosuppressant agents were noted. RESULT: A total of 42 children were included, 23 (54.7%) males and 19 (45.2%) were females. Jaundice was seen in all patients (100%) followed by acholic stools (81%). Associated malformations were noted in 6 (14.2%) patients. Liver function tests confirmed obstructive cholestasis (p 0.04). Kasai was done in 19 (45%) patients only, living donor liver transplant was performed in 6 (14%) patients. Age range of transplant patients was from 3 months to 1 year. Indication for liver transplant was failed Kasai in 1(16.7%) patient and chronic liver disease in 5 (83.3%) patients. LDLT survivors were 10 months to 1 year of age at the time of transplant, mean age was 10.6 months. Maximum survival noted so far is 7 years. Acute complications seen post-transplant were sepsis (three patients), surgical site infections (two patients), biliary leaks and acute cellular rejection in one patient each. Chronic graft rejection, portal vein stricture needing stenting was done in one patient. DISCUSSION: All patients underwent LDLT from related donors wih no donor related mortality. All are deceased patients were yonger and had advanced disease. BA remains third most commo indication of transplant in our center. CONCLUSION: Liver transplant is the only lifesaving procedure after failed Kasai or as primary liver transplant due to advance liver disease. The advent of liver transplantation services offers survival and improving outlook of the disease.

Heterologous expression of bacterial dehydrin gene in Arabidopsis thaliana promotes abiotic stress tolerance.

Salinity, low temperature, and drought are major environmental factors in agriculture leading to reduced crop yield. Dehydrins (DHNs) are induced transcriptionally during cellular dehydration and accumulate in different tissues during abiotic stresses. Here we isolated and characterized a bacterial gene BG757 in Arabidopsis, encoding a putative dehydrin type protein. ABA induces the expression of various dehydrins in plants, therefore, to elucidate the potential role, ABA sensitivity was examined in Arabidopsis transgenic lines expressing BG757. Interestingly, BG757-expressing plants showed hypersensitivity towards NaCl and ABA during seed germination. In addition to germination, BG757-expressing plants also showed root growth retardation in the presence of ABA and NaCl when compared with wild type (WT), suggesting that BG757 positively regulate salt stress and ABA response. Furthermore, BG757-expressing plants showed significant drought tolerance compared with WT. Consistent with drought tolerance, expression levels of stress inducible genes (DREB2A, RD22, RD26, LEA7 and SOS1) were strongly upregulated in transgenic plants compared with WT. All together these results suggest that heterologous expression of bacterial gene, BG757 in plants promotes resistance to environmental stresses. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01358-w.

Choledochal Cyst in Children, presentation and outcome - 10 years' experience from a tertiary care center in Pakistan.

Objectives: This study was done to compare the clinical features, laboratory findings and surgical outcomes of pediatric patients with choledochal cysts. Methods: Retrospective review of the hospital records of all pediatric patients admitted with choledochal cysts from 2011 to 2021 were collected and analyzed. Patients were divided into two groups; infant (less than one year age) and pediatric (1 to 16 years) for statistical comparison of two groups. Result: The study included 34 children, 9 (26.5%) were infant (<1 year) and 25 (73.5%) were more than one year old. Mean age at diagnosis was 15 months with age ranging from 14 days to 16 years. Females were 19 (55.9%) and males were 15 (44.1%). Type-I choledochal cyst was the most common (73.5%), presentation followed by Type-IVA (26.5%) in our patients. Patients from infant group presented with jaundice in 7 (77.7%), and clay-colored stool in 3 (33.3%) as the most common clinical features, while abdominal pain (88%), vomiting (72%), fever (32%) and pancreatitis (32%) were the frequent presentations among older age group. Post-surgical complications of excision of choledochal cyst were observed in 4 (11.7%) patients. Conclusion: Choledochal cysts have variable presentations depending upon age of the patients. Complete surgical excision of choledochal cyst is the treatment modality of choice and timely surgical management can prevent complications.

Risk factors, types, and neuroimaging findings in Children with Cerebral Palsy.

Objectives: Cerebral palsy is a major cause of neurodisability in children in Pakistan. The study aims to evaluate the risk factors, types and neuroimaging findings in children with cerebral palsy. Methods: All children diagnosed with cerebral palsy, between 1-16 years presenting to Shifa community health center were enrolled from January 2020 to July 2021. Informed consent was taken from parents. Results: A total of 89 patients were included, 62 (69.7%) male and 27 (30.3%) females. Mean age was 4.4 ± 2.8 years. Majority of babies were born at term 74 (84%) and 15 were preterm (16%). Most of the patients were born in hospital 55 (62%), 13 (14%) were born at home. Mean birth weight was 2.3 ± 0.3. Consanguinity was present in 56 (62.9%). Birth asphyxia 38 (42.7%) was the most common cause of cerebral palsy. Maternal antenatal risk factors identified were anemia 13 (14.6%), PIH (9%) infections (6%) were significant risk factors (<0.05). Neuroimaging was done in 37 (38.7%) of the patients only. Conclusion: Male gender is more affected in our cohort. Maternal anemia, pregnancy induced hypertension and low birth weight are significant modifiable risk factors. Prevention of these can reduce the incidence of cerebral palsy.

Spectrum of acute, recurrent and chronic pancreatitis in children.

OBJECTIVE: To determine the clinical presentation, aetiology and outcome of pancreatitis in paediatric population. METHODS: The retrospective study was conducted at Shifa International Hospital, Islamabad, Pakistan, and comprised data of children with pancreatitis presenting between 2013 and 2018. Medical records were reviewed and findings of clinical, laboratory workup and management were noted on a specifically developed proforma. Data was analysed using SPSS 23. RESULTS: Of the 51 subjects, 28(54.9%) were boys. The overall mean age was 10.6±4.9 years. The most frequent clinical symptom was epigastric pain 39(76.5%). The most common aetiology was gallstones/pancreatic stones 19(37.25%). Mean hospital stay was 5.1±1.8 days, and it was longer in children aged up to 5 years compared to older children (p<0.05). Acute pancreatitis was seen in 23(45.09%) patients, followed by recurrent 19(37.25%) and chronic 9(17.64%). There was no mortality. CONCLUSIONS: Timely diagnosis and prompt management of haemodynamic status could lead to successful recovery without any serious complications in paediatric pancreatitis.

Etiology, clinical presentation, and outcome of children with fulminant hepatic failure: Experience from a tertiary center in Pakistan.

OBJECTIVES: To determine etiologies, clinical presentations and outcomes of children with fulminant hepatic failure in the first liver transplant center of Pakistan. METHODS: It was a retrospective, observational study, conducted in Paediatric Gastroenterology Department of Shifa International Hospital. Patients between one month to 16 years were included who fulfilled the Pediatric Acute Liver Failure study group (PALFSG) definition of acute liver failure as biochemical evidence of liver injury with no known co-existing chronic liver disease, coagulopathy not corrected by vitamin K, an International Normalized Ratio (INR) greater than 1.5 if the patient has encephalopathy, or greater than 2.0 if the patient does not have encephalopathy. The data collected was recorded on a self-constructed proforma after IRB approval. RESULTS: There were 28 patients in the study which ncluded 17 males and 11 females with a mean age of 72.86±52.50 months. The most common etiologies were Hepatitis A (29%) in isolation or co-infection with Wilson Disease, typhoid fever. It was followed by seronegative hepatitis (29%). Majority (64%) had acute presentation (7 to 28 days), jaundice (82%) being the most common symptom. Severity of encephalopathy was significantly associated with outcome (p=0.02). There were 6 (21%) patients who succumbed to death. CONCLUSIONS: The study highlights infective diseases as the predominant etiology causing fulminant liver failure in children. Our study highlights lower mortality in children.

Case report on Ansa Pancreatica: An Uncommon Cause Accounting for Recurrent Pancreatitis in Children.

Acute recurrent pancreatitis is a rare entity in children. It can be caused by a number of reasons, anatomical variations being one of them. Panctreatica divisum is the most common form of ductal anomaly while ansa pancreatica has been the least studied and explored. In recurrent pancreatitis, Ansa Pancreatica was recently found to be a key risk factor. It is usually found among adult alcoholics. We submit the report of a rare but important cause of acute recurrent pancreatitis; an 11-year-old child with 2 previous episodes of pancreatitis was diagnosed with ansa pancreati ca on magnetic resonance cholangiopancreatography (MRCP). He was advised to get stenting of Pancreatic duct. To the best of our belief, only another case has been reported in the paediatric population.

Molecular charactarization of wheat advanced lines for leaf rust resistant genes using SSR markers.

A total of fifty seven wheat advanced lines were screened to detect the existence of leaf rust resistant genes (Lr9, Lr13, Lr19, Lr24, Lr26, Lr28, Lr32, Lr34, Lr35, Lr36, Lr37, Lr39 and Lr46) using thirteen SSR markers. Only four markers for Lr13, Lr32, Lr34 and Lr35 produced separate, reproducible bands which indicated the positive linkage of leaf rust resistance with these SSR markers. The highest frequency was observed for Lr32 (100%), as it was detected in all fifty seven lines, followed by Lr34 (89.4%) in 51 lines, Lr35 (87.7%) in 50 lines and Lr13 (31.5%) in 18 lines respectively. All the four resistant genes were identified in fifteen lines which is only 26% of the studied population. These results indicate that there are limited number of variant genes for leaf rust resistance in the studied wheat advanced lines. Therefore, strategies for arraying these genes to lengthen infection resistance are advised to eliminate wheat rust diseases. In addition, more reliable and capable markers are essential to be settled for marker assisted selection of these and other genes.

Genetic Polymorphism and Bottleneck Analysis of Balkhi, Hashtnagri, and Michni Sheep Populations Using Microsatellite Markers.

Pakistan is rich in sheep genetic resources. Balkhi, Hashtnagri, and Michni are neighboring sheep populations found in Khyber Pakhtunkhwa province of Pakistan. In this study, we analyzed the genetic structures and bottleneck incidents within these sheep populations using 31 microsatellite DNA markers. Total numbers of 116, 100, and 95 alleles, with average numbers of 3.20, 3.26, and 3.74 alleles per locus were observed, respectively, in Balkhi, Hashtnagri, and Michni population. Mean observed heterozygosity was 0.402 in Balkhi, 0.416 in Hashtnagri, and 0.522 in Michni population. All the three sheep populations showed significantly high inbreeding. Michni population was found to be in mutation drift equilibrium, showing the absence of genetic bottleneck. The data of Balkhi and Hashtnagri indicated the presence of genetic bottleneck in these populations. These results suggest a moderate level of genetic diversity within Michni population that may be useful for breed improvement programs. Hashtnagri and Balkhi populations having low within breed genetic variability may contain some valuable characteristics that need to be conserved.

Spectrum of histopathological diagnosis in paediatric patients with liver disorders in Pakistan.

OBJECTIVE: To document spectrum of paediatric liver disorders confirmed on liver biopsy. METHODS: The retrospective review of patients was conducted at Shifa International Hospital, Islamabad, Pakistan, and comprised data of all children who underwent ultrasound-guided percutaneous liver biopsy between December 2008 and June 2015. Frequency of individual diagnosis was assessed and compared on gender basis. SPSS 16 was used for statistical analysis. RESULTS: There were medical records of 74 patients in the study with an overall median age of 6.9 years (interquartile range: 0.2-17.7 years). Metabolic 27(36.5%) and inflammatory 19(25.6%) disorders were the most common aetiologies. At presentation 29(39.1%) patients had cirrhosis; and 25(34%) children were <5 years of age. Metabolic disorders were the most common aetiology in children upto 10 years of age with 19(25.6%) patients. Above the age of 10 years, inflammatory disorders were more frequent and were seen in 10(13.5%). Based on gender, a trend towards significance was observed for metabolic disorders (p=0.08) and children who presented with cirrhosis (p= 0.07), but it was not statistically significant. CONCLUSIONS: Metabolic disorders were the most common cause of liver disorders. A number of children at presentation had underlying cirrhosis.

Auxiliary partial orthotopic liver transplant for Criggler-Najjar Syndrome: Report of 2 cases from Pakistan.

Auxiliary partial orthotopic liver transplant (APOLT) is a treatment option for certain liver disorders where liver structure is preserved. It includes Criggler Najjar syndrome (CNS), urea cycle defects and familial hypercholesterolaemia. Liver transplant as a treatment modality has only recently become available in Pakistan. Here we report two paediatric cases of CNS type 1 where auxiliary liver transplant was performed to correct jaundice and prevent inevitable brain damage. Both recipients and their respective living donors had successful surgery and are doing well.

The Hidden Source of Testosterone Hypersecretion in a Female-A 30-Year Journey.

A Sertoli-Leydig cell tumor (SLCT) is a rare ovarian tumor that often excessively secretes testosterone and its precursor, leading to virilization in females. We present a case of a female patient with persistent, severe hyperandrogenism. Our patient had a history of left oophorectomy due to an ectopic pregnancy and initially presented with amenorrhea at the age of 30. Biochemical evaluations suggested ovarian hyperandrogenism. Despite the absence of an ovarian mass, she underwent a right oophorectomy and remained hyperandrogenic postoperatively. When she established care with our endocrinology clinic at the age of 58, she had more virilizing features and total testosterone levels ranging from 10.1 to 12.0 nmol/L (292-346 ng/dL; normal reference range for women: 0.07-1.56 nmol/L; 2-45 ng/dL). While biochemical evaluations were consistent with tumorous ovarian hyperandrogenism, ultrasound and computed tomography again failed to identify the source. Finally, an 18F-fluorodeoxyglucose-positron emission tomography/computed tomography revealed a mass in the left adnexa, and she underwent removal of the mass. The final pathology confirmed SLCT. The case highlights that SLCT may be small and slow-growing and not readily visible on conventional imaging modalities.

A Rare Case of Giant Bilateral Adrenal Myelolipomas in a Patient With Classical Congenital Hyperplasia.

Congenital adrenal hyperplasia (CAH) is caused by genetic defects in the enzymes involved in cortisol biosynthesis in the adrenal gland and, in more than 90% of cases, due to a deficiency in the 21-hydroxylase enzyme. Classical CAH due to 21-hydroxylase deficiency is a severe form of the disease that presents with cortisol deficiency and is further categorized into salt-wasting or simple-virilizing types. Appropriate steroid replacement has been shown to effectively treat patients with classical CAH and prevent complications. Individuals who receive inadequate treatment or fail to comply with their prescribed steroid hormone regimen are susceptible to the development of adrenal myelolipomas. Myelolipomas are benign tumors composed of both adipose and hematopoietic tissues. While documented cases of adrenal myelolipomas exist in medical literature, instances of large bilateral myelolipomas remain exceedingly rare. This case report highlights a 40-year-old female patient with a known history of classical congenital adrenal hyperplasia who presented with unusually large bilateral adrenal myelolipomas. A diagnostic CT scan of the abdomen and pelvis revealed a 13.4 x 10.8 cm myelolipoma on the left adrenal gland and a 10 x 8.6 cm myelolipoma on the right adrenal gland. Prior to her presentation, the patient experienced recurrent nausea and vomiting, along with left upper quadrant pain, over five months. Hormonal assessments indicated significantly elevated serum androgen levels, suggesting inadequate management of her CAH. In this report, we present a rare case of symptomatic bilateral large adrenal myelolipomas, underscoring the significance of adhering to treatment regimens, diagnostic assessments, and management for adrenal myelolipomas in individuals diagnosed with CAH.

Rice seeds biofortification using biogenic iron oxide nanoparticles synthesized by using Glycyrrhiza glabra: a study on growth and yield improvement.

Iron, a crucial micronutrient, is an integral element of biotic vitality. The scarcity of iron in the soil creates agronomic challenges and has a detrimental impact on crop vigour and chlorophyll formation. Utilizing iron oxide nanoparticles (IONPs) via nanopriming emerges as an innovative method to enhance agricultural efficiency and crop health. The objective of this study was to synthesize biogenic IONPs from Glycyrrhiza glabra (G. glabra) plant extract using green chemistry and to evaluate their nanopriming effects on rice seed iron levels and growth. The synthesized IONPs were analyzed using UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), Transmission electron microscopy (TEM), and Energy-dispersive X-ray (EDX) techniques. The UV-Vis peak at 280 nm revealed the formation of IONPs. SEM and TEM showed that the nanoparticles were spherical and had an average diameter of 23.8 nm. Nanopriming resulted in a substantial enhancement in growth, as seen by a 9.25% and 22.8% increase in shoot lengths for the 50 ppm and 100 ppm treatments, respectively. The yield metrics showed a positive correlation with the concentrations of IONPs. The 1000-grain weight and spike length observed a maximum increase of 193.75% and 97.73%, respectively, at the highest concentration of IONPs. The study indicates that G. glabra synthesized IONPs as a nanopriming agent significantly increased rice seeds' growth and iron content. This suggests that there is a relationship between the dosage of IONPs and their potential for improving agricultural biofortification.

Spectrum of Pediatric Autoimmune Hepatitis in a Cohort of Pakistani Children.

Background. Autoimmune hepatitis (AIH) is increasingly seen in children worldwide and it is more severe in children compared to adults. This study highlights the biochemical and clinical aspect, treatment given and outcome of the disease including pediatric liver transplantation. Study. Retrospective review (2012-2022) was done in Shifa International Hospital, Islamabad. Patients under 18 years diagnosed with AIH were included. Data related to age, gender, clinical features, laboratory investigations including liver function test, liver biopsy findings and imaging modalities were included. Results. Fifteen patients were included 7 (47%) were males and 8 (53%) females. AIH type 1 was the most common type seen in 7 (46%), AIH type 2 in 5 (33%) and seronegative in 3 (20%). Jaundice was the most common symptom. Liver biopsy showed findings characteristic of AIH. Liver transplant performed in 3 patients. Conclusion. The study highlights the varied clinical presentation of AIH in Pakistani children.

Green Fabrication, Characterization of Zinc Oxide Nanoparticles Using Plant Extract of Momordica charantia and Curcuma zedoaria and Their Antibacterial and Antioxidant Activities.

In recent years, the rapid increase in the resistance of microorganisms to antibiotics has produced major health issues. Novel applications for these compounds have been developed by integrating modern technologies such as nanotechnology and material science with the innate antibacterial activity of metals. The current study demonstrated the synthesis of zinc oxide nanoparticles (ZnO NPs) from Momordica charantia and Curcuma zedoaria plant extracts, as well as their antibacterial properties. The synthesis of ZnO NPs was confirmed via UV-visible spectroscopy, showing clear peaks at 375 and 350 nm for M. charantia and C. zedoaria, respectively. Scanning electron microscopy (SEM) analysis revealed crystals of irregular shapes for the majority of the nanoparticles synthesized from both plants. The existence of ZnO NPs was confirmed using X-ray diffraction while the particle size was calculated using Scherrer's equation, which was 19.65 for C. zedoaria and 17.02 for M. charantia. Different functional groups were detected through Fourier transform infrared spectroscopy analysis. The antibacterial activity of the ZnO NPs at three different concentrations (250, 500, and 1000 µg/ml) was assessed against three different bacterial strains, i.e., Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa), using disc diffusion methods. The ZnO nanoparticles showed promising antibacterial activity against bacterial strains. For C. zedoaria, the highest growth inhibition was observed at a concentration of 1000 µg/ml, which was 18, 19, and 18 mm as compared to antibiotics (15, 11, and 15.6 mm) against E. coli, P. aeruginosa, and S. aureus, respectively. Similarly, at 1000 µg/ml of NPs, M. charantia showed the highest growth inhibition (18, 15, and 17 mm) as compared to antibiotics (15, 11, and 14.6 mm) against E. coli, P. aeruginosa, and S. aureus, respectively. In conclusion, compared to pure plant extract and antibiotics, ZnO NPs at a higher concentration (1000 µg/ml) exhibited a significant difference in zone of inhibition against all the bacterial strains. Different concentrations of ZnO using M. charantia and C. zedoaria caused increments in the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The nanoparticles extracted using C. zedoaria exhibited higher antioxidant activity than M. charantia. Greenly synthesized ZnO nanoparticles have remarkable antibacterial properties and antioxidant activity, making them a promising contender for future pharmaceutical application.

Detrimental effects of Cd and temperature on rice and functions of microbial community in paddy soils.

Heavy metal (HM) contamination and high environmental temperature (HT) are caused by anthropogenic activities that negatively impact soil microbial communities and agricultural productivity. Although HM contaminations have deleterious effects on microbes and plants; there are hardly any reports on the combined effects of HM and HT. Here, we reported that HT coupled with cadmium (Cd) accumulation in soil and irrigated water could seriously affect crop growth and productivity, alternatively influencing the microbial community and nutrient cycles of paddy soils in rice fields. We analyzed different mechanisms of plants and microflora in the rhizospheric region, such as plant rhizospheric nitrification, endophytes colonization, nutrient uptake, and physiology of temperature-sensitive (IR64) and temperature-resistant Huanghuazhan (HZ) rice cultivars against different Cd levels (2, 5 and 10 mg kg-1) with rice plants grown under 25 °C and 40 °C temperatures. Consequently, an increment in Cd accumulation was observed with rising temperature leading to enhanced expression of OsNTRs. In contrast, a greater decline in the microbial community was detected in IR64 cultivar than HZ. Similarly, ammonium oxidation, root-IAA, shoot-ABA production, and 16S rRNA gene abundance in the rhizosphere and endosphere were significantly influenced by HT and Cd levels, resulting in a significant decrease in the colonization of endophytes and the surface area of roots, leading to a decreased N uptake from the soil. Overall, the outcomes of this study unveiled the novel effects of Cd, temperature, and their combined effect on rice growth and functions of the microbial community. These results provide effective strategies to overcome Cd-phytotoxicity on the health of endophytes and rhizospheric bacteria in Cd-contaminated soil by using temperature-tolerant rice cultivars.

Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries.

OBJECTIVES: Vitamin D dependent rickets type 1A (VDDR1A) is a rare autosomal recessive condition due to inactivating mutation of CYP27B1. It mimics clinically, biochemically and rediologically to nutritional and hypophosphatemic rickets. In developing countries like Pakistan, VDDR1A is often misdiagnosed as nutritional rickets or hypophosphatemic rickets due lack of free access to 1,25 (OH) 2 D level and genetic testing. This study was aimed to determine the clinical spectrum and diagnostic challenges of VDDR1A due to CYP27B1 mutation in developing countries. METHODS: Retrospective review of all cases of VDDR1A due to CYP27B1 mutation over a period of two years presenting in the Pediatric Endocrine clinic of Hameed Latif Hospital, Lahore, Pakistan. RESULTS: Six cases of VDDR1A (4 males) were identified. Mean age of clinical manifestation was 14 (9-24) months. Mean age of presentation to endocrine department was 5.5 (1.5-11.8) years. Growth failure and bony deformities were the most common presentation (n=6), followed by repeated diarrheas and abdominal distension (n=3) and recurrent fractures (n=1). All cases shared same biochemical profile of low/normal calcium, hypophosphatemia, raised alkaline phosphatase, raised PTH, normal/high 25(OH)D and tubular reabsorption of phosphate (TRP) <85%. Patients treated with calcitriol showed rapid healing as compared to those treated with 1-alfacalcidol. CONCLUSIONS: We should have a high index of suspicion of VDDR1A in rickets not responding to cholecalciferol therapy.