Klotho in pregnancy and intrauterine development - Potential clinical implications: a review from the European Renal Association CKD-MBD Working Group.

Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared to maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis, and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intra-uterine growth restriction, and an increased perinatal risk for newborns, indicating a potential used of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use.

Sublingual prophylactic administration of OVA-loaded MSC-derived exosomes to prevent allergic sensitization.

AIM: This study evaluated the immunomodulatory and delivery potential of adipose tissue-isolated MSC-derived exosomes as a prophylactic regimen through a sublingual route in the ovalbumin (OVA)-induced allergic asthma murine model. MATERIAL AND METHODS: Balb/c mice received 10 µg/dose of OVA-enriched MSC-derived exosomes as a prophylactic regimen in six doses during three weeks, and then OVA sensitization was conducted through intraperitoneal and aerosol administration of allergen. The total cells and eosinophils counted in nasal lavage fluid (NALF) and lung tissues were assessed for histopathological analysis. In addition, the secretion of IFN-γ, IL-4, and TGF-ß by spleen cells and serum OVA-specific IgE levels were measured via ELISA. RESULTS: Significant reduction in the IgE levels and IL-4 production, along with elevated TGF-ß levels, were observed. Also, limited cellular infiltrations and perivascular and peribronchiolar inflammation in the lung tissues and normal total numbers of cells and eosinophils in the NALF were reported. CONCLUSION: Prophylactic regimen using OVA-enriched MSC-derived exosomes modulated immune responses and inhibited allergic OVA sensitization.

From transabdominal to totally extra-peritoneal robotic ventral hernia repair: observations and outcomes.

PURPOSE: While robotic-assisted hernia repair has increased the popularity of minimally invasive hernia surgery, selecting between the types of approaches is a challenge for both experts and novices alike. In this study, we compared a single surgeon's early experience transitioning from transabdominal hernia repair with sublay mesh in either the pre-peritoneal or retrorectus space (TA-SM) and enhanced-view totally extra-peritoneal (eTEP) ventral hernia repair in the peri-operative and long-term post-operative time periods. METHODS: We conducted a retrospective review of 50 eTEP and 108 TA-SM procedures to collect demographics, intraoperative details, and 30-day and 1-year post-operative outcomes. Statistical analysis was performed utilizing Chi-square analysis, Fisher's test, and two sample t-tests with equal variances. RESULTS: There were no significant differences in patient demographics or comorbidities. eTEP patients had larger defects (109.1 cm2 vs. 31.8 cm2, p = 0.043) and mesh used (432.8 cm2 vs. 137.9 cm2, p = 0.001). Operative times were equivalent (158.3 ± 90.6 min eTEP and 155.8 ± 65.2 min TA-SM, p = 0.84), but conversion to alternate procedure type was higher for the transabdominal approach (4% eTEP vs. 22% TA-SM, p < 0.05). Hospital stay was less in the eTEP cohort (1.3 days vs. 2.2 days, p < 0.05). Within 30 days, there were no significant differences in emergency visits or hospital readmissions. There was a greater propensity for eTEP patients to develop seromas (12.0% vs. 1.9%, p < 0.05). At 1 year, there was no statistically significant difference in recurrence rate (4.56% eTEP vs. 12.2% TA-SM, p = 0.28) respective to average time to recurrence (9.17 months eTEP vs. 11.05 months TA-SM). CONCLUSION: The eTEP approach can be adopted safely and efficiently, and may have superior peri-operative outcomes including fewer conversions and reduced hospital stay.

Immune response modulation by allergen loaded into mesenchymal stem cell-derived exosomes as an effective carrier through sublingual immunotherapy.

BACKGROUND: Allergen-specific sublingual immunotherapy (SLIT) was considered an interesting needle-free alternative for subcutaneous immunotherapy (SCIT). Mesenchymal stem cell (MSC)-derived exosomes were introduced as potent nanoscale delivery systems with immunomodulatory potentials. The current study investigated the therapeutic efficacy of SLIT using ovalbumin (OVA)-enriched MSC-derived exosomes formulation in a murine model of allergic asthma. MATERIAL AND METHODS: MSCs were harvested from mice adipose tissues. Then, exosomes were isolated, and OVA-loaded exosomes were prepared. Following sensitization, Balb/c mice received therapeutic formulation (10 µg/dose OVA-containing MSC-derived exosomes) twice a week for two months. Serum OVA-specific IgE levels as well as IFN-γ, IL-4, and TGF-ß secretions by cultured splenocytes were measured by ELISA. Also, lung tissue underwent histopathologic analysis, and the numbers of inflammatory cells and eosinophils in nasopharyngeal lavage fluid (NALF) were examined. RESULTS: SLIT using OVA-enriched exosomes significantly reduced IgE levels and IL-4 production, while the secretion of IFN-γ and TGF-ß were significantly elevated. Also, a decrease was observed in the numbers of total cells and eosinophils in the NALF, and lower levels of perivascular and peribronchiolar inflammation and cellular infiltrations were observed in the lung tissue. CONCLUSION: SLIT using OVA-loaded exosomes improved immunomodulatory responses and efficiently alleviated allergic inflammation.

The Effect of Nano Calcium Carbonate and/or Recombinant Bone Morphogenetic Protein as a Biological Orthodontic Retainer on the Body Weight of Experimental Rat.

BACKGROUND: Retention after orthodontic tooth movement (OTM) is essential to prevent relapse. This study examined the effects of a fixed orthodontic device and Nano Calcium Carbonate (CaCO3) nanoparticles with or without recombinant human bone morphogenetic protein (rhBMP) on rat body weight. MATERIALS AND METHODS: OTM was administered for 21 days to 80 Wistar Albino rats. First molar mesialization was active then forming two 40-rat groups which were subdivided into four subgroups of 10 rats each. These subgroups received 5 µg/kg rhBMP, 75 µg/kg CaCO3, 80 µg/kg rhBMP-loaded CaCO3 and one control. The relapse rate was examined weekly over the second 21 days when the second group exhibited mechanical retention and the first did not. Group 1 rats were murdered after 21 days (day 42), whereas group 2 rats entered a third 21-day post-retention period and then murdered (day 63). BW and OTM were measured on days 1, 21, 28, 35, 42, and 63. RESULTS: Within each group, the animal body weight was reduced significantly after the intervention and continued over time with a higher average reduction in the 9-week group than the 6-week group. However, there were no significant (P-value ˃0.05) differences in the BW between the groups of the two (6-week and 9-week) sets and the subgroups of the 6-week set across each time point. In contrast, there was a significant (P-value ˂0.05) difference between the BW of the conjugate subgroup and the other three subgroups in the 9-week set, particularly on 63rd day. CONCLUSION: CaCO3 nanoparticles and/or BMP with orthodontic treatment collectively or individually cause a reduction of body weight in rats.

Allergen specific immunotherapy with plasmid DNA encoding OVA-immunodominant T cell epitope fused to Tregitope in a murine model of allergy.

BACKGROUND: Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy. METHODS: Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined. RESULTS: Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ, IL-10, and TGF-ß expression were increased. Moreover, OVA-specific IgE levels were also decreased. CONCLUSION: These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy.

CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor. This study aimed to investigate the gene and protein expression of RAP1GAP and DNA methylation patterns of its CpG74a , CpG74b , and CpG24 in an Iranian population with MTC. METHODS: In this case-control study, we selected 55 individuals who underwent thyroidectomy in Erfan hospital, Tehran, between 2018 and 2020. Samples were divided into normal thyroid tissues (control; n=20), benign nodule (n=20), and MTC (n=15). DNA methylation patterns were investigated using MSP (methylation-specific PCR). The protein level and mRNA expression of RAP1GAP were also evaluated using western blotting and real-time PCR, respectively. RESULTS: The hyper-methylation rates of CpG24 and CpG74a in the MTC samples were considerably higher than the controls (83% versus 15% and 74% versus 17%, respectively; P<0.001). The methylation/unmethylation ratio of CpG74a , and CpG24 was considerably higher than the controls (P<0.001). The methylation/unmethylation ratio of CpG24 in the benign nodules was also considerably greater than the controls (P<0.001). The mRNA expression and the protein level of RAP1GAP in the MTC group were considerably lower than the controls (P=0.005 and P=0.035, respectively). In the MTC group, aberrant methylation of CpG74a and CpG24 was significantly correlated with decreasing expression of the Rap1Gap gene (R2 : 0.23; P=0.032 and R2 : 0.56; P=0.001, respectively). CONCLUSION: Hyper-methylation in CpG24 and CpG74a and decreasing expression of RAP1GAP can be considered as diagnostic biomarkers for MTC.

Tranilast as an Adjunctive Therapy in Hospitalized Patients with Severe COVID- 19: A Randomized Controlled Trial.

BACKGROUND: Tranilast is a potential NLRP3 inflammasome inhibitor that may relieve progressive inflammation due to COVID-19. AIM OF THE STUDY: To evaluate the therapeutic effects of Tranilast in combination with antiviral drugs in non-ICU-admitted hospitalized patients with COVID-19. METHODS: This study was an open-label clinical trial that included 72 hospitals admitted patients with severe COVID-19 at Razi Hospital, Ahvaz, Iran, from July 2020-August 2020. These patients were randomly assigned in a 1:1 ratio to control (30) and intervention groups (30). Patients in the control group received antiviral therapy, while patients in the intervention group received Tranilast (300 mg daily) in addition to the antiviral drugs for Seven days. The collected data, including the expression of inflammatory cytokine, laboratory tests, and clinical findings, was used for intragroup comparisons. RESULTS: The intervention group showed significantly lower levels of NLR (p = 0.001), q-CRP (p = 0.002), IL-1 (p = 0.001), TNF (p = 0.001), and LDH (p = 0.046) in comparison with the control group. The effect of intervention was significant in increasing the o2 saturation (F = 7.72, p = 0.007). Long hospitalization (four days or above) was 36.6% in the Tranilast and 66.6% in the control group (RR = 0.58; 95% CI: 0.38-1.06, p = 0.045). In the Tranilst and control groups, one and four deaths or hospitalization in ICU were observed respectively (RR = 0.31; 95% CI: 0.03-2.88, p = 0.20). CONCLUSIONS: Tranilast might be used as an effective and safe adjuvant therapy and enhance the antiviral therapy's efficacy for managing patients with COVID-19.

Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial.

The present study conducted a placebo-controlled clinical trial to evaluate the impact of nano-curcumin on the inflammatory cytokines in mild-to-moderate hospitalized COVID-19 patients. A total of 60 COVID-19 patients were randomly divided into nano-curcumin and control groups, and then they received 240 mg/day nano-curcumin for 7 days. The clinical manifestation and laboratory parameters in patients were recorded on days 0 and seven. Also, SYBR Green real-time PCR and ELISA techniques were implicated in assessing the mRNA expression of IFN-γ, IL-1ß, IL-6, MCP-1, and TNF-α and the serum levels of IL-1ß, IL-6, and TNF-α inflammatory mediators, respectively. Although the clinical manifestations and laboratory parameters improved via the nano-curcumin treatment, the mRNA expression of IFN-γ (p = 0.006) and TNF-α (p = 0.04) were significantly reduced. Besides, a considerable difference was observed between the nano-curcumin and control groups in the expression of IFN-γ (p = 0.001), IL-1ß (p = 0.0002), and IL-6 (p = 0.008). In addition, there was a significant difference between the nano-curcumin and control groups in the serum levels of IL-1ß (p = 0.042). The evidence demonstrated that nano-curcumin could be implicated as a complementary medication to act as an antiinflammatory agent and inhibit inflammatory complications.

Molecular diagnosis of maturity onset diabetes of the young in Iranian patients: improving management.

BACKGROUND: The purpose of this study is to identify the mutations of the most common form of maturity-onset diabetes of the young (MODY), also known as MODY3, in diabetic patients suspected of MODY. This can recommend appropriate medical surveillance of at-risk family members of MODY based on the genetic cause. METHODS: We analyzed the clinical course of 19 patients from 12 unrelated Iranian families with diabetes features. The coding regions and intron-exon boundaries of the hepatocyte nuclear factor 1 alpha (HNF1A) gene were studied by polymerase chain reaction (PCR) and sanger sequencing. Also, the detected mutation was analyzed by bioinformatics tools. RESULTS: One novel frameshift insertion mutation (p.Glu11Argfs*12) was detected in one of the probands and seven other patients of her family with the heterozygote state. The mutation is located in the exon1 of the dimerization domain of the HNF1A gene. According to the In Silico analysis, the detected mutation is predicted as a pathogenic one. CONCLUSIONS: Differential diagnosis between MODY3 and other forms of diabetes can be considered a necessity in terms of overlapping symptoms of MODY3 with type1 or 2 diabetes. Molecular genetic testing can provide an accurate diagnosis for optimal management.

RAP1GAP Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer.

Inactivation of tumor suppressor genes, such as RAP1GAP, by hypermethylation of their regulatory region can give rise to thyroid tumors. The aim of this study was to investigate the expression of the RAP1GAP gene and the DNA methylation patterns of its CpG74a, CpG74b, and CpG24 in an Iranian population with differentiated thyroid cancer (DTC). In this study, 160 individuals who underwent thyroidectomy in the Tehran Erfan Hospital between 2018 and 2020 were selected. DNA methylation patterns of selected CpG islands (CpG74a, CpG74b, and CpG24) were determined using methylation-specific PCR. The mRNA expression and protein level of -RAP1GAP were also evaluated. SW1736 and B-CPAP cells were treated with 5-aza-2'-deoxycytidine (5-Aza) to demethylate these regions. The hypermethylation rates of CpG74a and CpG24 in DTC samples were significantly higher than in the control. The mRNA expression and protein level of -RAP1GAP were significantly decreased in the DTC group. In the DTC group, hypermethylation in CpG74a was correlated with decreasing RAP1GAP expression (R2: 0.34; p = 0.043). CpG74a with a specificity of 86.4% has significant prediction power to distinguish between DTC and normal thyroid tissues. Additionally, hypermethylation of CpG74a was significantly associated with higher tumor stages (stage III-IV: 77%; stage I-II: 23%; p = 0.012). Increasing expression of RAP1GAP after demethylation with 15 µM of 5-Aza was observed in both cell lines. These results indicate that DNA hypermethylation in CpG74a can be considered as an epigenetic biomarker in DTC.

Metal-coded hydrogel magnetic molecularly imprinted polymer for preconcentration and cleanup of sarcosine: Determination in urine; coupled to on-column capillary electrophoresis.

In this study, sarcosine metal-coded hydrogel magnetic molecularly imprinted polymer (Hydro-MeC-MMIP) has been fabricated and coupled to on-column derivatization capillary electrophoresis (CE). As a metal-coding approach, sarcosine-Cu2+-ligand (Sar-Cu2+-L) chelate complex was introduced as a template to overcome the problems associated with the fabrication of MMIP for a small molecule having limited functional groups such as sarcosine. To our best knowledge, it is the first time that methacrylamide (MA) coated Fe3O4 (Fe3O4@MA) with abounded reactive double-bound on the surface has been used as a magnetic core in the one-pot synthesis of MMIPs. As prepared, Hydro-MeC-MMIP was characterized by different microscopic, spectroscopic, and thermal gravimetric methods. Hydro-MeC-MMIP was used to extract and preconcentrate sarcosine in the urine sample with no treatment and dilution. Sarcosine was quantified by on-column derivatization capillary electrophoresis equipped with a photodiode array detector. A mixture of thirteen amino acids was separated with a total run time of 12 min. Three structural analogs, including alanine, sarcosine, and glycine, were significantly resolved. Under optimal experimental conditions, the method's detection and quantification limits were 9.93 and 33.10 ng mL-1, respectively. The linear range of 50-2000 ng mL-1 and 96% recovery, along with the relative standard deviation of 6.07% (n = 6) for the target amino acid, were obtained. This method provides a simple, low-cost, fast, and efficient tool for extracting and quantifying sarcosine in the urine. The present method can address inconsistency in evaluating sarcosine as a candidate biomarker for prostate cancer with a simple CE/UV; no need for a sophisticated detection system such as a mass spectrometer.

Specifying of aquifer characteristics using forward and inverse modeling of DC-resistivity and TEM methods.

Exploration and determination of the hydro-geo-electrical characteristics of an aquifer can be done by applying the forward (initial multi-layers), and the inverse (final layered) models for interpreting the DC-resistivity (VES) and TEM data. So, 22 VES using Schlumberger configuration (AB/2 = 500-700m) and 12 TEMS using in-loop configuration (square, ℓ = 200m) were carried out at the West El-Minia selected area for studying the Oligocene Clastic and Carbonate aquifers. VESs were interpreted for studying the shallow resistive and conductive layers, as well as faults delineation. TEMs were interpreted for shallow and deep conductive layers discrimination. The VES and TEM inverse models were examined with the drilling data and construed the subsurface into four units; dry Oligocene Clastics (173-467 Ω.m), dry limestone (273-374 Ω.m), saturated Oligocene Clastics (Oligocene aquifer) (2-107 Ω.m), then saturated fractured Eocene limestone to shaly limestone (5-188 Ω.m). Groundwater depths (62-131m) and thicknesses variation were estimated, as well as the faults location. Two hydro-geo-electrical sections were built for simulating the resistivity values and their connotations, and managing in choosing the promised locations for drilling wells. The ramp-off time effect was studied and found that ∼50-∼100m shallow high resistive thickness didn't defined from the TEM data in which the max penetration depth was 672m. The available well logging data were analysed to reveal the pure saturated zones, the volume of shale of 0%-100% and the porosity values of ∼9%-∼35% in the Oligocene aquifer and of ∼4%-∼15.5% in the carbonate aquifer. So, the forward and inverse models application and soundings integration are considered robust tools for estimating and simulating the aquifer characteristics.

Comparing Oxidative Stress Status Among Iranian Males and Females with Malignant and Non-malignant Thyroid Nodules.

BACKGROUND: Oxidative stress is commonly accrued in thyroid tissue during hormone synthesis. OBJECTIVES: We aimed to examine oxidative stress in patients with thyroid cancer, benign thyroid nodules, and healthy individuals. METHODS: In this study, 138 individuals were involved. Among the selected participants, 108 had thyroid nodules, including 30 papillary thyroid cancer (PTC), 30 follicular thyroid cancer (FTC), six anaplastic thyroid cancer (ATC), 12 medullary thyroid cancer (MTC), and 30 benign nodules. In addition, 30 individuals were selected as a healthy control group. The levels of total antioxidant capacity (TAC) and total oxidant status (TOS) of thyroid tissue were measured using the ELISA method, and the oxidative stress index (OSI) was calculated. RESULTS: The TAC level was significantly lower in MTC and FTC subtypes than in controls. The TOS level was considerably higher in the MTC group than in the control and benign nodule groups. The TOS level was not changed in other groups. The OSI was considerably higher in MTC and FTC subtypes. The TAC and OSI in benign nodules were significantly lower and higher than those of controls, respectively. The OSI was higher in female patients than in males. CONCLUSIONS: The OSI can not be considered a diagnostic biomarker for benign nodules and MTC. The diverse oxidative stress status between genders may be related to the elevated cancer incidence in females.

Are asymptomatic gastrointestinal findings on imaging more common in COVID-19 infection? Study to determine frequency of abdominal findings of COVID-19 infection in patients with and without abdominal symptoms and in patients with chest-only CT scans.

PURPOSE: To identify incidence of abdominal findings in COVID-19 patients with and without abdominal symptoms on various imaging modalities including chest-only CT scans and to correlate them with clinical, laboratory and chest CT findings. MATERIALS AND METHODS: In this retrospective study, we searched our clinical database between March 1st, 2020 and May 22nd, 2020 to identify patients who had positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat swabs for COVID-19, had availability of clinical, laboratory information and had availability of CT scan of chest or abdominal radiograph, abdominal ultrasound or CT scan within 2 weeks of the diagnosis. Abdominal imaging findings on all imaging modalities were documented. Chest CT severity score (CT-SS) was assessed in all patients. Clinical and laboratory findings were recorded from the electronic medical record. Statistical analysis was performed to determine correlation of abdominal findings with CT-SS, clinical and laboratory findings. RESULTS: Out of 264 patients with positive RT-PCR, 73 patients (38 males and 35 females; 35 African American) with mean age of 62.2 (range 21-94) years were included. The median CTSS was 13.5 (IQR 75-25 18-8). Most common finding in the abdomen on CT scans (n = 72) were in the gastrointestinal system in 13/72 patients (18.1%) with fluid-filled colon without wall thickening or pericolonic stranding (n = 12) being the most common finding. Chest-only CT (n = 49) found bowel findings in 3 patients. CTSS did not differ in terms of age, sex, race or number of comorbidities but was associated with longer duration of hospitalization (p = 0.0.0256), longer intensive care unit stay (p = 0.0263), more frequent serum lactate dehydrogenase elevation (p = 0.0120) and serum C-reactive protein elevation (p = 0.0402). No statistically significant correlation of occurrence of bowel abnormalities with CTSS, clinical or laboratory features. Deep venous thrombosis was seen in 7/72 patients (9.8%) with three patients developing pulmonary embolism CONCLUSION: Abnormal bowel is the most common finding in the abdomen in patients with COVID-19 infection, is often without abdominal symptoms and occurs independent of severity of pulmonary involvement, other clinical and laboratory features.

Non-traumatic Tension Gastrothorax: A Potential Mimicker of Tension Pneumothorax.

Tension gastrothorax is a rare, life-threatening clinical condition caused by intrathoracic herniation of the stomach through a diaphragmatic defect which becomes increasingly distended over time. If not recognized promptly, this can rapidly progress to respiratory distress, mediastinal shift, and hemodynamic compromise. Initial clinical presentation and imaging findings closely mirror those of tension pneumothorax, confounding diagnosis and potentially leading to unnecessary interventions with increased risk of morbidity and mortality. Here, we present a case of an elderly female who presented with a non-traumatic tension gastrothorax and a review of key imaging features and strategies to aid in recognition and accurate diagnosis of this emergent clinical entity.

Robotic ventral hernia repair: a safe and durable approach.

BACKGROUND: Short-term success following robotic-assisted ventral hernia repair (RVHR) is well established; however, data describing outcomes after the first year are limited. In this study, we followed a cohort of patients with an average of 1.8 years of follow-up to demonstrate the durability of this technique and examine risk factors for recurrence. METHODS: A retrospective analysis of RVHR performed by a single surgeon from 2012 to 2016 was done. The technical approach for hernia repair consisted of tension-free primary fascial closure with placement of preperitoneal mesh when possible. The primary end point of hernia recurrence was determined based on physical examination or imaging documented in the medical record. A logistic regression model was used to identify patient risk factors for recurrence. RESULTS: One hundred and eight RVHRs were performed over 4 years. Mean age was 52.72 ± 13.61 years, BMI was 33.07 ± 7.82 kg/m2, and hernia defect size was 70.1 ± 86.3 cm2. In terms of patient characteristics, 17.6% of patients were diabetic, 13.9% were smokers preoperatively, 72.2% were ASA class 3 or higher, and 29.6% had prior VHR. Primary fascial closure was achieved in all RVHRs, with 23.1% requiring component separation. Mesh was used in 97.2% of patients: 79.5% had preperitoneal mesh and 17.6% had intraperitoneal onlay mesh. Ninety-eight percent of patients had long-term follow-up at a mean of 625.6 days. Recurrence rate was 12%, with one recurrence attributed to an inguinal hernia fixed concurrently with a midline defect. There were no statistically significant differences in gender, age, BMI, ASA class, incidence of diabetes, smoking status, or number of previous hernia repairs. Hernia defect size and perioperative complications including SSO, ileus, obstruction, or any other medical complication were not predictive of recurrence. Technical approach did not affect outcomes. CONCLUSION: RVHR is safe and durable with a low recurrence rate at a mean of 21 months postoperatively. Patient characteristics or type of repair were not predictive of recurrence.

Identification of Cytochrome b-245, beta-chain gene mutations, and clinical presentations in Iranian patients with X-linked chronic granulomatous disease.

BACKGROUND: X-linked chronic granulomatous disease (X-CGD) is an immunodeficiency disorder caused by defects in the gp91phox subunit that leads to life-threatening infections. We aimed to identify CYBB gene mutations and study clinical phenotypes in Iranian patients with probable X-CGD. METHODS: We studied four unrelated Iranian patients with probable X-CGD and their families recruited in several years. We isolated genomic DNA from whole blood and performed Sanger sequencing in the CYBB gene's coding and flanking regions. We also performed pathogenicity predictions using in silico tools. RESULTS: We detected four different mutations, including a novel insertion mutation in exon 5 (p.Ile117AsnfsX6), in the patient. Bioinformatics analysis confirmed the pathogenic effect of this mutation. We predicted protein modeling and demonstrated lost functional domains. The patient with the insertion mutation presented pneumonia and acute sinusitis during his life. We also detected three other known nonsense mutations (p.Arg157Ter, p.Arg226Ter, and p.Trp424Ter) in the CYBB gene. The patient with p.Arg157Ter developed lymphadenitis and pneumonia. Moreover, the patient with inflammatory bowel disease showed p.Arg226Ter and the patient with tuberculosis presented p.Trp424Ter. We detected different clinical features in the patients compared to other Iranian patients with the same mutations. CONCLUSION: Our results expand the genetic database of patients with X-CGD from Iran and make it much easier and faster to identify patients with X-CGD. Our results also help to detect carriers and enable prenatal diagnosis in high-risk families as a cost-effective strategy.

Impact of assessing smile parameters as part of orthodontic treatment planning - a survey based analysis.

BACKGROUND: Smile forms an imporatnt aspect of facial analysis, as it contributes to overall facial esthetics. Many orthodontists pay more attention to cephalometric radiograph; and profile assessment to improve their patients' esthetics; however, the facial attractiveness of the individuals is obviously improved through enhancing their smiles. This study was aimed at evaluating the impact of analyzing certain smile esthetic parameters on diagnosis and treatment plan for individuals seeking orthodontic treatment. MATERIALS AND METHODS: An electronic questionnaire with 24 questions arranged on five main axes was designed. These axes included smile arc, smile line, buccal corridors, smile symmetry, and photographic analysis of the smile, with several questions in each axis. The electronic link of the questionnaire was sent to all members of the Iraqi Orthodontic Society in April 2019. The answers were collected after 4 weeks of questionnaire link distribution date. RESULTS: Among the surveyed orthodontists, there was a consistent agreement to assess the smile arc, smile line, buccal corridors, and smile symmetry, with main axes scores (4.14 ± 0.81, 4.1 ± 0.79, 3.86 ± 0.82, and 4.16 ± 0.86 respectively). Moreover, the participants prefer, with 3.89 ± 0.86 main axis score, to use the facial photograph for a less time-consuming and detailed evaluation of smile features. CONCLUSIONS: Smile parameters, for example, smile arc, smile line, buccal corridors, and smile symmetry are better to be analyzed using photographs during orthodontic diagnosis and treatment planning.