Exogenously applied nicotinic acid alleviates drought stress by enhancing morpho-physiological traits and antioxidant defense mechanisms in wheat.

Across the globe, the frequent occurrence of drought spells has significantly undermined the sustainability of modern high-input farming systems, particularly those focused on staple crops like wheat. To ameliorate the deleterious impacts of drought through a biologically viable and eco-friendly approach, a study was designed to explore the effect of nicotinic acid on different metabolic, and biochemical processes, growth and yield of wheat under optimal moisture and drought stress (DS). The current study was comprised of different levels of nicotinic acid applied as foliar spray (0 g L-1, 0.7368, 1.477, 2.2159 g L-1) and fertigation (0.4924, 0.9848, and 1.4773 g L-1) under normal conditions and imposed drought by withholding water at anthesis stage. The response variables were morphological traits such as roots and shoots characteristics, yield attributes, grain and biological yields along with biosynthesis of antioxidants. The results revealed that nicotinic acid dose of 2.2159 g L-1 out-performed rest of treatments under both normal and DS. The same treatment resulted in the maximum root growth (length, fresh and dry weights, surface area, diameter) and shoot traits (length, fresh and dry weights) growth. Additionally, foliar applied nicotinic acid (2.2159 g L-1) also produced as the highest spike length, grains spike-1, spikelet's spike-1 and weight of 1000 grains. Moreover, these better yield attributes led to significantly higher grain yield and biological productivity of wheat. Likewise in terms of physiological growth of wheat under DS, the same treatment remained superior by recording the highest SPAD value, relative water content, water potential of leaves, leaf area, stomatal conductance (292 mmolm-2S-1), internal carbon dioxide concentration, photosynthesis and transpiration rate. Interestingly, exogenously applied nicotinic acid remained effective in triggering the antioxidant system of wheat by recording significantly higher catalase, peroxidase, superoxide dismutase and ascorbate peroxidase.

Transhiatal versus Left Transthoracic Esophagectomy for Gastroesophageal Junction Cancer; The Impact of Surgical Approach on Postoperative Complications.

BACKGROUND Esophagectomy is the mainstay of treatment for esophageal cancer. Although different surgical approaches have been described, choosing the most appropriate technique is still on debate. We compared the complications of transhiatal esophagectomy (THE) versus left transthoracic esophagectomy (LTE) among a group of Iranian patients with gastroesophageal junction cancer. METHODS This was a retrospective study between 2011 and 2013 on 40 patients with gastroesophageal cancer. 23 patients underwent THE and the others underwent LTE. 30-day postoperative mortality, complications, duration of hospital stay, and number of dissected lymph nodes were studied. RESULTS 37.5% of the patients had squamous cell carcinoma. No mortality was seen. Totally, 10 patients suffered from complications. Cardiac and pulmonary complications occurred in eight and six patients, respectively. No patients suffered from vocal cord injuries and anastomotic leakage. The mean duration of postoperative hospital stay was 11.82 ± 3.8 days, and the mean number of dissected lymph nodes was 8.2 ± 3.9. No significant difference was seen between the two groups (p > 0.05). CONCLUSION Choosing between the approaches for resection of gastroesophageal cancer may not impact the complications and mortality rates. We propose that LTE approach could be used safely in comparison with THE, and that selecting between THE and LTE may be based on the surgeon's preference and experience.

IL-22 in hepatocyte's survival of Pakistani patients with end stage liver disease: an insight into IL 22 mediated hepato-regenerative pathway.

Hepatitis is the principal cause of hepatocellular carcinoma (HCC) and decompensated cirrhosis. HCC is amongst the leading causes of deaths worldwide. Current therapeutic options have proven to be unsuccessful in treating this disease due to multifactorial nature of the disease. The present study was designed to investigate the role of IL-22 mediated survival of hepatocytes during cirrhosis and HCC. Resected/explanted liver tissue samples of patients with End Stage Liver Disease were obtained from Hepato-Pancreato-Biliary Liver Transplant Unit of Sheikh Zayed Hospital, Lahore, Pakistan. Qualitative expression of IL-22, SOCS3, and IL-22 induced anti-apoptotic protein, B-cell lymphoma extra-large (Bcl-xL), were evaluated by Immunohistochemical analysis (IHC). The IHC analysis revealed significantly high expression of IL-22, SOCS3, and Bcl-xL within explanted livers of HCC patients. Overall, the expression of SOCS3 was higher than any other protein, and the expression of all proteins showed significant variation in different group of patients based on clincopathological features. The results of the current study indicated that IL-22 mediated JAK-STAT pathway i.e. liver regeneration and healing is dependent on the disease progression and type of agent responsible for causing the infection in the first place. However, quantitative analysis of these factors in future can provide further evidence of the role of this pathway in HCC for development of anti-HCC therapies.

Clinical outcome of thymectomy in myasthenia gravis patients: A report from Iran.

Background: Myasthenia gravis (MG) is an autoimmune disease affecting acetylcholine postsynaptic receptor of voluntary muscles. Thymectomy is done in these patients and is a mainstay in the treatment of MG; however, the long-term result of surgery is still controversial. This study dealt with the investigation of the results of thymectomy in treatment, recovery and control of the symptoms of these patients. Methods: This study was performed through a retrospective method in patients suffering from MG who underwent trans-sternal thymectomy between 2011 and 2016. We conducted thymectomy, excision of mediastinal mass and contents of tissues between the right and left phrenic nerves for all patients. Then, the effect of various variables including age, sex, time interval between onset of disease and surgery, thymus pathology and the dosage of drug on clinical response after surgery was determined using various statistical tests. Results: 47 patients including 26 men and 21 women with the mean age of 33.0 ± 4.6 years have been investigated. The mean age of patients was 36.2 and 29.7 in men and women respectively (P = 0.041). Spiral chest computed tomography (CT) scan was present in 47 patients demonstrating mediastinal mass in 40 (85.1%) patients. Also, our pathological results showed thymic cells in aortopulmonary window contents of 4 patients. According to the results, the younger age of patients at the time of surgery, shorter time between diagnosis and thymectomy, being a woman and non-thymoma pathology were along with better clinical outcomes after thymectomy. Conclusion: Our study shows better clinical results of thymectomy in patients with normal chest CT scan and normal or atrophic thymus in pathologic reports. Generally, it seems that performing thymectomy in a shorter time interval after diagnosis of MG is beneficial. Moreover, in MG patients who do not suffer from thymoma, it is along with positive results.

Complete excision of large invasive retroperitoneal paraganglioma mislabelled as hypertrophic obstructive cardiomyopathy.

Paraganglioma originates from chromaffin cells of adrenal medulla and autonomic paraganglia, which are derived from the neural crest cells. Paragangliomas are half as common as pheochromocytomas with 69% occurring in head and neck, 22% in abdomen and pelvis and 10% in the thorax. About 70% paragangliomas are sporadic, 30% are hereditary, having identifiable germline mutations of Succinate Dehydrogenase enzyme (SDH).

Molecular diagnosis of primary immunodeficiency diseases in a developing country: Iran as an example.

Primary immunodeficiency diseases (PID) comprise a heterogeneous group of inherited diseases with a wide spectrum of clinical manifestations and laboratory abnormalities. Definite diagnosis of a PID is performed most reliably by detection of a gene mutation which will allow genetic counseling. In addition, detection and confirmation of PIDs that were not severe enough during childhood to lead to a specific diagnosis would be possible. As a definite diagnosis of PID is of importance for the management of these disorders, we present a review on studies that have investigated mutations among patients with different types of PID in Iran. Although the frequency of a definite molecular diagnosis of PID in Iran is acceptable in a developing country, we believe that providing additional laboratory resources and diagnostic methods, development of specialized centers for PID, in addition to improvement of physicians' awareness, may facilitate clinical and genetic diagnosis of patients with PID in Iran.

Identification of recurrent c.742G>T nonsense mutation in ECM1 in Pakistani families suffering from lipoid proteinosis.

Lipoid proteinosis (LP) is one of the rare, recessive autosomal disorders clinically characterized by widespread deposition of hyaline-like material in the skin, mucosa and viscera. Classical features include beaded eyelid papules, laryngeal infiltration and hoarseness of voice caused by pathogenic mutations in the ECM1 gene located on 1q21.2. In present study ethnically different, three consanguineous Pakistani families with typical cutaneous features of LP were analysed to investigate the underlying molecular basis. PCR based linkage analysis using microsatellite markers localized the families to locus 1q21.2, harboring ECM1 gene. To identify the mutation in the candidate gene (ECM1), Sanger sequencing was carried out. All the families were found to carry c.742 G>T nonsense mutation in exon 7 of the ECM1 gene that resulted in a truncated ECM1 protein containing 247 amino acids instead of 540 (p.E248X). To further investigate the impact and importance of mutation in LP pathogenesis we applied different bioinformatics tools. In silico studies has predicted lack of functional domains and 65 % shorter ECM1 mutant protein. It is the first report of recurrence mutation from Pakistan as c.742G>T nonsense mutation was found in three ethnically different Pakistani families with LP. Study strengthens the conclusion that c.742G>T mutation is the pathological cause of LP. Furthermore, data also support the fact that exon 7 is one of the most common hot spots of pathological mutations in ECM1. The absence of functional domains and truncated sequence most likely contribute to the lack of ECM1 function and thereby influence several aspects of dermal homeostasis that leads to LP pathogenesis.

In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum.

BACKGROUND: Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation. RESULTS: The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving XPA gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation (c.654del A) in exon 5 of XPA gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 (p.Lys218AsnfsX5). In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. In silico analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system. CONCLUSIONS: Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain.

Synchronous presentation of acute acalculous cholecystitis and appendicitis: a case report.

INTRODUCTION: Acute acalculous cholecystitis is traditionally associated with elderly or critically ill patients. CASE PRESENTATION: We present the case of an otherwise healthy 23-year-old Caucasian man who presented with acute right-sided abdominal pain. An ultrasound examination revealed evidence of acute acalculous cholecystitis. A laparoscopy was undertaken and the dual pathologies of acute acalculous cholecystitis and acute appendicitis were discovered and a laparoscopic cholecystectomy and appendectomy were performed. CONCLUSION: Acute acalculous cholecystitis is a rare clinical entity in young, healthy patients and this report describes the unusual association of acute acalculous cholecystitis and appendicitis. A single stage combined laparoscopic appendectomy and cholecystectomy is an effective treatment modality.

Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family.

UNLABELLED: Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family. METHODS: Genotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to the ECM1 gene. To screen for mutations in the ECM1 gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer. RESULTS: The results revealed linkage of the LP family to the ECM1 locus. Sequence analysis of the coding exons and splice junctions of the ECM1 gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at amino acid position 206. CONCLUSIONS: The finding of a novel mutation in Pakistani family extends the body of evidence that supports the importance of ECM1 gene for the development of lipoid proteinosis.

Tacrolimus rescue therapy for corticosteroid-resistant and polyclonal antibody-resistant kidney allograft rejections.

INTRODUCTION: The conventional treatment of acute kidney allograft rejection consists of high-dose corticosteroids and polyclonal antibodies. We report our experience of tacrolimus rescue therapy in patients with acute rejections refractory to corticosteroids and polyclonal antibodies. MATERIALS AND METHODS: A total of 34 patients with a mean age of 42.3 years and clinical diagnosis of acute kidney allograft rejection underwent tacrolimus rescue therapy when treatment with corticosteroids and polyclonal antibodies failed. Kidney allograft biopsy results were available in 21 patients. All of the patients received tacrolimus, 0.1 mg twice daily, and in those who responded to the therapy after 4 to 6 months, tacrolimus was changed into cyclosporine. RESULTS: Pathologic examination of 21 biopsy specimens of the kidney allografts showed acute vascular rejection in 7 patients (33.3%), acute humoral rejection in 6 (28.6%), acute cellular rejection in 3 (14.3%), and accelerated acute rejection in 3 (14.3%). Twenty-six patients (76.5%) responded to rescue therapy with tacrolimus and discharged with a mean serum creatinine level of 1.4 mg/dL (range, 1.1 mg/dL to 1.7 mg/dL). Allograft nephrectomy was done in 8 patients (23.5%) because of no response to treatment of rejection, the pathology reports of which consisted of acute vascular rejection in 5 patients and extensive necrosis in 3. CONCLUSION: Tacrolimus therapy is able to salvage kidney allografts with acute refractory rejection. We recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy. However, severe infectious complications as a result of overt immunosuppression must be considered.