Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Incidence of infection in carpal tunnel surgery with and without the use of local antibiotics.

Objectives: To compare the infection rate in patients who underwent carpal tunnel surgery with and without instilling local antibiotics into the surgical wound. METHODS: The retrospective cohort study was conducted at the Department of Surgery, Unit of Neurosurgery, Government Naseer Ullah Babar Memorial Hospital, Peshawar, Pakistan, and comprised data from July 2019 to July 2021 related to non-diabetic patients without any comorbidity who had undergone fresh carpal tunnel surgery. The cases had been operated by two surgeons having a different approach to preventing infection in carpal tunnel surgery cases. The surgeon in group A did not use any local antibiotics after completing the surgery, while the surgeon in group B instilled local gentamicin in the open wound for 3 minutes after completing the nerve release. All patients were put on oral antibiotics for a period of 5 days after the procedure in both the cohorts, and were assessed fortnightly for any infection and removal of stitches. Demographics of the patients, use of antibiotics and the occurrence of infection were recorded on a proforma. Data was analysed using SPSS 20. RESULTS: Of the 177 patients operated during the period, 13(7.3%) were discarded owing to missing data. Of the 164(92.7%) patients analysed, 138(84.14%) were females and 26(15.85%) were males. The overall mean age was 32.46±8.97 years. The total surgeries conducted were 176; 96(54.54%) in group A and 80(45.45%) in group B. Infections were found in 3(1.7%) patients; all in group A (p=0.160). CONCLUSIONS: Although not statistically significant, instillation of local antibiotics may play a role in preventing surgical site infections in carpal tunnel surgery cases.

In-vitro Augmentation of Mesenchymal Stem Cells by Using Adult Bovine Serum.

BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are increasingly being utilized for immune-related disease therapies due to their low immunogenicity. However, the primary culture of UC-MSCs requires the supplementation of serum in the growth medium, which has posed a challenge due to ethical issues related to the collection method of the fetal bovine serum (FBS) that is routinely used in cell culture. AIM: In order to address this, the purpose of this research was to assess the effectiveness of adult bovine serum (ABS) as a different and more affordable source of serum for the in-vitro cultivation of UC-MSCs. UC-MSCs were isolated from the umbilical cord of Wharton's jelly of cow immediately after birth, by digestion with Collagenase type I. METHOD: ABS was collected from fresh bovine sources and heat-inactivated. The morphology of UC-MSCs was observed under an inverted microscope, and growth patterns, proliferative index, and doubling time were calculated every two days to compare the efficacy of ABS with FBS. Immunocytochemistry for specific markers was also conducted on the MSCs. RESULT: The results showed a notable difference in morphology, growth rate, population doubling, and proliferative index between ABS and FBS. CONCLUSION: Intriguingly, ABS proved to be an effective supplement in the growth medium for expanding UC-MSCs in vitro, providing a viable alternative to FBS.

Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract.

Congenital cataract (CC) causes a third of the cases of treatable childhood blindness worldwide. CC is a disorder of the crystalline lens which is established as clinically divergent and has complex heterogeneity. This study aimed to determine the genetic basis of CC. Whole blood was obtained from four consanguineous families with CC. Genomic DNA was extracted from the blood, and the combination of targeted and Sanger sequencing was used to identify the causative gene. The mutations detected were analyzed in silico for structural and protein-protein interactions to predict their impact on protein activities. The sequencing found a known FYCO1 mutation (c.2206C>T; p.Gln736Term) in autosomal recessive mode in families with CC. Co-segregation analysis showed affected individuals as homozygous and carriers as heterozygous for the mutation and the unaffected as wild-type. Bioinformatics tools uncovered the loss of the Znf domain and structural compactness of the mutant protein. In conclusion, a previously reported nonsense mutation was identified in four consanguineous families with CC. Structural analysis predicted the protein as disordered and coordinated with other structural proteins. The autophagy process was found to be significant for the development of the lens and maintenance of its transparency. The identification of these markers expands the scientific knowledge of CC; the future goal should be to understand the mechanism of disease severity. Ascertaining the genetic etiology of CC in a family member facilitates establishing a molecular diagnosis, unlocks the prospect of prenatal diagnosis in pregnancies, and guides the successive generations by genetic counseling.

Designing Highly Photoactive Hybrid Aerogels for In-Flow Photocatalytic Contaminant Removal Using Silica-Coated Bacterial Nanocellulose Supports.

This study explores the use of silica-coated bacterial nanocellulose (BC) scaffolds with bulk macroscopic yet nanometric internal pores/structures as functional supports for high surface area titania aerogel photocatalysts to design flexible, self-standing, porous, and recyclable BC@SiO2-TiO2 hybrid organic-inorganic aerogel membranes for effective in-flow photo-assisted removal of organic pollutants. The hybrid aerogels were prepared by sequential sol-gel deposition of the SiO2 layer over BC, followed by coating of the resulting BC@SiO2 membranes with a porous titania aerogel overlayer of high surface area using epoxide-driven gelation, hydrothermal crystallization, and subsequent supercritical drying. The silica interlayer between the nanocellulose biopolymer scaffold and the titania photocatalyst was found to greatly influence the structure and composition, particularly the TiO2 loading, of the prepared hybrid aerogel membranes, allowing the development of photochemically stable aerogel materials with increased surface area/pore volume and higher photocatalytic activity. The optimized BC@SiO2-TiO2 hybrid aerogel showed up to 12 times faster in-flow photocatalytic removal of methylene blue dye from aqueous solution in comparison with bare BC/TiO2 aerogels and outperformed most of the supported-titania materials reported earlier. Moreover, the developed hybrid aerogels were successfully employed to remove sertraline drug, a model emergent contaminant, from aqueous solution, thus further demonstrating their potential for water purification.

Size Control and Improved Aqueous Colloidal Stability of Surface-Functionalized ZnGa2O4:Cr3+ Bright Persistent Luminescent Nanoparticles.

Near-infrared (NIR)-emitting ZnGa2O4:Cr3+ (ZGO) persistent luminescent nanoparticles (PLNPs) have recently attracted considerable attention for diverse optical applications. The widespread use and promising potential of ZGO material in different applications arise from its prolonged post-excitation emission (several minutes to hours) that eliminates the need for continuous in situ excitation and the possibility of its excitation in different spectral regions (X-rays and UV-vis). However, the lack of precise control over particle size/distribution and its poor water dispersibility and/or limited colloidal stability required for certain biological applications are the major bottlenecks that limit its practical applications. To address these fundamental limitations, herein, we have prepared oleic acid (OA)-stabilized ZGO PLNPs with controlled size (7-12 nm, depending on the type of alcohol used in synthesis) and monodispersity. A further increase in size (8-21 nm), with a concomitant increase in persistent luminescence, could be achieved using a seed-mediated approach, employing the as-prepared ZGO PLNPs from the first synthesis as the seed and growing layers of the same material by adding fresh precursors. To remove their surface oleate groups and make the nanoparticles hydrophilic, two surface modification strategies were evaluated: modification with only poly(acrylic acid) (PAA) as the hydrophilic capping agent and modification with either PAA or cysteamine (Cys) as the hydrophilic capping agent in conjunction with BF4- as the intermediate surface modifier. The latter surface modifications involving BF4- conferred long-term (60 days and longer) colloidal stability to the nanoparticles in aqueous media, which is related to their favorable ζ potential values. The proposed generalized strategy could be used to prepare different kinds of surface-functionalized PLNPs with control of size, hydrophilicity, and colloidal stability and enhanced/prolonged persistent luminescence for diverse potential applications.

Association between 17q21 variants and asthma predisposition in Pashtun population from Pakistan.

OBJECTIVE: Asthma is a heterogeneous and genetically complex respiratory disease, and more than 300 million people are affected worldwide. In this study, frequencies of four SNPs (rs3816470, rs7216389, rs8067378, rs12603332) in chromosome 17q21 region were analyzed and their relationship with the asthma susceptibility, in the Pashtun population of Khyber Pakhtunkhwa province (KPK) of Pakistan were investigated. METHODS: DNA samples from 500 subjects (asthma cases/controls) were genotyped by Sanger sequencing. Chi-square tests, logistic regression analysis, linkage disequilibrium, and haplotype analysis techniques were applied to study the association of the SNPs with asthma. RESULTS: Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive, were tested. The frequencies of alleles T/T at rs3816470 (OR = 1.91; 95%CI = 1.15-3.18; p = .011*) and rs7216389 (OR = 2.14; 95%CI = 1.21-3.79; p = .0076*), A/A at rs 8067378 (OR = 1.89; 95%CI = 1.17-3.06; p = .0081*), C/C at rs12603332 (OR = 1.97; 95%CI = 1.18-3.27; p = .008*), under recessive models, respectively, were significantly (p-values < .0125) associated with asthma susceptibility. The frequencies of T/T genotype in rs3816470 (OR = 6.01; 95%CI = 2.48-14.60; p = .000147*), and rs7216389 (OR = 5.05; 95%CI = 1.79-14.21; p = .003296*), and C/C at rs12603332 (OR = 2.64; 95%CI = 1.11-6.32; p = .019063*), were significantly (p-values < .0125) associated with asthma susceptibility in Pashtun women by stratified analysis based on age and gender. Similarly, three unique haplotypes were found associated with disease development and protective effect in female and male subjects. Linkage disequilibrium analysis presented a strong linkage (≥80%) between SNP variants and predicted their co-inheritance in the studied population. CONCLUSION: The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly (p-values < .0125) associated with asthma predisposition in the Pashtun population of KPK exclusively in the female asthmatic cases.Supplemental data for this article can be accessed.

Supported nanostructured photocatalysts: the role of support-photocatalyst interactions.

Heterogeneous photocatalysis employing semiconductor oxide photocatalysts is a sustainable and promising method for environmental remediation and clean energy generation. In this context, nanostructured photocatalysts, with at least one dimension in the 1‒100 nm size regime, have attracted ever-growing attention due to their unique and often enhanced size-dependent physicochemical properties. While their reduced size ensures enhanced photocatalytic performance, the same makes it difficult and time/energy-demanding to remove/recover such nanostructured photocatalysts from aqueous media. This fundamental limitation has paved the way towards developing supported nanophotocatalysts where the active photocatalytic nanostructures are coated on the surface of polymeric or inorganic support materials, often in a core@shell conformation. This arrangement solves the problem of photocatalysts' recovery for effective reuse or recycling and leads to improved and desired target properties due to specific photocatalyst-support interactions. While the enhanced physicochemical properties of supported photocatalysts have been widely studied in many target applications, the role of support-photocatalysts interactions in improving these properties remains unexplored. This review article provides an updated viewpoint on the photocatalyst-support interactions and the resulting unique physiochemical properties important for diverse photochemical applications and the design of practical devices. While exploring the properties of supported nanostructured metal oxide/sulfides photocatalysts such as TiO2 and MoS2, we also briefly discuss the common strategies employed to coat the active nanomaterials on the surface of different supports (organic/polymeric, inorganic, active, inert, and magnetic).

Unusual Local Therapies Used for the Treatment of Low Back Pain and Sciatica: Concepts and Approaches.

Background and objective Low back pain (LBP) and sciatica are major healthcare issues globally. Since patients may seek various ways to cure their ailments, these conditions are managed not just by physicians, but many other health-related professionals provide alternative treatment options for it as well. We conducted this study to examine a local subset of patients who used stabbing their back and legs as a treatment option for curing LBP and sciatica. Materials and methods This cross-sectional study was conducted in the outpatient clinic of the Neurosurgery unit of Government Naseer Ullah Babar Memorial Hospital, Peshawar, Pakistan, from July 2019 to March 2020. Patients who presented to the outpatient department (OPD) with complaints of LBP with or without sciatica, with a history of invasive therapy in the form of stabbing the back or leg, or drawing blood from the veins of the lower limbs, were included. All other patients with LBP seeking neurosurgical advice were excluded from the study. The study was approved by the management of the hospital and informed consent was obtained from the patients before interviewing them. Special permission was taken for publishing the photographs. The demographics and clinical information related to patients, such as age, gender, duration of symptoms, time since the local therapy, particulars of the treatment provider, any relief experienced by the patient, duration of relief, the patient beliefs/notions about the therapy and disease, and education level of the patients, were recorded on a predesigned form after taking informed consent. The study was done on purposive sampling. The data was presented in tables and charts and was analyzed using SPSS Statistics version 20 (IBM, Armonk, NY). Results During the study period, more than 8,000 patients visited the neurosurgical OPD, and the majority of them (>70%) sought treatment for LBP and sciatica. Of them, around 130 patients had a history of undergoing some alternative therapy that is not scientifically proven, and it was either in the form of stabbing the back or drawing blood from the veins in the lower limbs. Amongst these patients, almost 80% were males and 20% were females who had undergone this kind of treatment. The age range among the cohort was 25-68 years and the mean age was around 43 years. The duration of symptoms ranged from two months to nine years, and the time since the therapy and patient seeking medical advice ranged from three months to 4.5 years. The treatment had been provided by a local individual who did not hold any medical degree according to the patients in 100% (n=130) of the cases; 67% of patients felt they had experienced some relief from the therapy for a short period, which ranged from three days to one month. About the condition, none of the patients seeking the therapy knew it was nerve-related and were often confused about the term rugg (vessel in the native language) but could not differentiate it from the nerve. Of these patients, 76 required surgery while 54 were managed conservatively for LBP and sciatica. Conclusion A subset of the local population in our part of the world used stabbing the back and leg as a form of therapy for treating the problems of the lower back and sciatica. This has not been previously reported and has no scientific basis. Also, the majority of the patients were uneducated and had very little knowledge of the disease, and the treatment provider was a non-health-related professional.

Duration of In-hospital Stay for Elective Neurosurgical Procedures in a Tertiary Care Hospital.

OBJECTIVE: Public hospitals have fixed days with allotted time slots during which to perform neurosurgical elective cases. If emergency operations or other events preempt these scheduled time slots, the patient remains hospitalized, waiting in queue for a new time slot. We conducted this study to determine the number of days patients remained admitted waiting for elective cases in a tertiary care public hospital, which operates on fixed days. MATERIALS AND METHODS: This cross-sectional study was conducted in the Department of Neurosurgery Unit B, Medical Teaching Institution (MTI) - Lady Reading Hospital (LRH), Peshawar. We reviewed the admission charts and discharge slips of all patients who were admitted and underwent operations between September 2018 and August 2019. A form was made and was completed with each patients' records like age, gender, number of days spent preoperatively and postoperatively and the total duration of stay, indication for surgery (spinal, cranial, peripheral nerve), etc. Patients who had undergone elective neurosurgical procedures were included while those who had undergone emergency surgeries or had expired during the hospital stay, had been discharged or referred to other centers were excluded from the study. All the data were entered into the statistical software SPSS version 22 (IBM Corp., Armonk, NY) and were converted into tables and charts. RESULTS: A total of 1818 patients were admitted/discharged during the study period, and of them, 823 patients were admitted for elective neurosurgical procedures. There were 601 (73.7%) males and 222 (26.3%) females with a male to female ratio of approximately 3:1. The age range was from 09 days to 72 years and was further subdivided into six groups. The procedures were broadly divided into cranial, spinal, related to hydrocephalus (HCP)-related, and miscellaneous. Cranial procedures comprised of surgeries for brain tumors, transsphenoidal operations, vascular procedures for aneurysms, and nerve decompressions, and they comprised about 29.43% (n=244) while spinal procedures accounted for 317 (36.63%) procedures, the rest were related to HCP and miscellaneous. Preoperative and postoperative stay durations were calculated and then added to determine the total stay durations and were further stratified for the specific procedures and categorized into days and weeks. About 58.26% (n=143) of cranial cases, and 156 (49.36%) of spinal cases, 37.57% (n=65) of HCP-related cases, and 36.66% (n=41) of cases in the miscellaneous group had a duration of stay between eight days to more than three weeks.

Early Complications of Ventriculoperitoneal Shunt in Pediatric Patients With Hydrocephalus.

Objective Ventriculoperitoneal shunt (VPS) is the most commonly used procedure for the treatment of hydrocephalus (HDC), especially in children. However, this is prone to many complications, and requires repeated surgeries, which as such increases the morbidity of the patients. It is estimated that majority of the complications occurs in the immediate post-operative period and the rate of complications decreases over the time, with no impunity to these, though. We conducted this study to know about the complications of VPS in the early post-operative period, in pediatric patients with hydrocephalus. Materials and methods This descriptive study was conducted in the Department of Neurosurgery, Lady Reading Hospital, Peshawar, between June 2019 and January 2020 (seven months). All patients with hydrocephalus below 12 years of age, operated for the first time were included after taking an informed consent, while those with repeated shunt procedures and elderly patients requiring shunt were excluded from the study. Patients' details like age, gender, location, contact number, cause of hydrocephalus, date of shunt placement, type of surgery (elective or emergency) and any follow-up complications like failure, erosion, infections, ileus were noted on a predesigned proforma. After the surgery, patients were followed for a period of one month, and contacted either through the telephone or asked to visit in the outpatients on the specified days, and were evaluated for any shunt-related complications, and any of these complications suspected were further evaluated and noted. The data was analyzed using the statistical program SPSS version 19 (IBM Corp., Armonk, NY). Results are presented in the form of charts, tables and graph. Results During the study period, we evaluated a total of 151 patients; there were 78 (51.65%) males and 73 (48.34%) females with a male to female ratio approaching 1.1:1. The age range was from 22 days to 12 years. The mean age was 38.46 ± 7.53 months. The primary indications for the insertion of VP shunt were: congenital hydrocephalus in 70 (46.4%), post infectious hydrocephalus in 57 (37.7%), hydrocephalus due to tumor in 22 (14.6%), and post traumatic hydrocephalus in two (1.4%) patients. Among the total number of patients, 85 patients (55.6%) were done as elective cases and 66 patients (44.4%) were done as emergency cases. Complications were encountered in 30 patients (19.87%) during the follow-up of 30 days. Complications occurred between day 1 and day 20 of follow-up with a mean of 9.10 ± 1.69 2SD days. Conclusion VP shunt is the most widely used treatment for HDC, but is predisposed to complications and almost every fifth case of VP shunt comes across with complications. Shunt blockage, infections and abdominal wound-related complications are common earlier complications in pediatric patients with hydrocephalus.

Bacterial Nanocellulose/MoS2 Hybrid Aerogels as Bifunctional Adsorbent/Photocatalyst Membranes for in-Flow Water Decontamination.

To address the problems associated with the use of unsupported nanomaterials, in general, and molybdenum disulfide (MoS2), in particular, we report the preparation of self-supported hybrid aerogel membranes that combine the mechanical stability and excellent textural properties of bacterial nanocellulose (BC)-based organic macro/mesoporous scaffolds with the excellent adsorption-cum-photocatalytic properties and high contaminant removal performance of MoS2 nanostructures. A controlled hydrothermal growth and precise tuning of the synthetic parameters allowed us to obtain BC/MoS2-based porous, self-supported, and stable hybrid aerogels with a unique morphology resulting from a molecular precision in the coating of quantum-confined photocatalytic MoS2 nanostructures (2-4 nm crystallite size) on BC nanofibrils. These BC/MoS2 samples exhibit high surface area (97-137 m2·g-1) and pore volume (0.28-0.36 cm3·g-1) and controlled interlayer distances (0.62-1.05 nm) in the MoS2 nanostructures. Modification of BC with nanostructured MoS2 led to an enhanced pollutants removal efficiency of the hybrid aerogels both by adsorptive and photocatalytic mechanisms, as indicated by a detailed study using a specifically designed membrane photoreactor containing the developed photoactive/adsorptive BC/MoS2 hybrid membranes. Most importantly, the prepared BC/MoS2 aerogel membranes showed high performance in the photoassisted in-flow removal of both organic dye (methylene blue (MB)) molecules (96% removal within 120 min, Kobs = 0.0267 min-1) and heavy metal ions (88% Cr(VI) removal within 120 min, Kobs = 0.0012 min-1), separately and/or simultaneously, under UV-visible light illumination as well as excellent recyclability and photostability. Samples with interlayer expanded MoS2 nanostructures were particularly more efficient in the removal of smaller species (CrO42-) as compared to larger (MB) dye molecules. The prepared hybrid aerogel membranes show promising behavior for application in in-flow water purification, representing a significant advancement in the use of self-supported aerogel membranes for photocatalytic applications in liquid media.

A novel nonsense mutation in the STS gene in a Pakistani family with X-linked recessive ichthyosis: including a very rare case of two homozygous female patients.

BACKGROUND: X-linked ichthyosis (XLI; OMIM# 308100) is a recessive keratinization disorder characterized by the presence of dark brown, polygonal, adherent scales on different parts of the body surface. It almost exclusively affects males and the estimated prevalence ranges from 1:2000-6000 in males worldwide. Extracutaneous manifestations are frequent including corneal opacities, cryptorchidism, neuropsychiatric symptoms or others. Up to 90% of XLI cases are caused by recurrent hemizygous microdeletion encompassing entire STS gene on chromosome Xp22.3, while only a minority of patients shows partial deletions or loss of function point mutations in STS. Larger deletions also involving contiguous genes are identified in syndromic patients. METHODS: Here, we report clinical and genetic findings of a large Pakistani family having 16 affected individuals including 2 females with XLI. Molecular karyotyping and direct DNA sequencing of coding region of the STS gene was performed. RESULTS: The clinical manifestations in affected individuals involved generalized dryness and scaling of the skin with polygonal, dark scales of the skin on scalp, trunk, limbs, and neck while sparing face, palms and soles. There were no associated extra-cutaneous features such as short stature, cryptorchidism, photophobia, corneal opacities, male baldness, and behavioral, cognitive, or neurological phenotypes including intellectual disability, autism or attention deficit hyperactivity disorder. Molecular karyotyping was normal and no copy number variation was found. Sanger sequencing identified a novel hemizygous nonsense mutation (c.287G > A; p.W96*), in exon 4 of STS gene in all affected male individuals. In addition, two XLI affected females in the family were found to be homozygous for the identified variant. CONCLUSIONS: This study is useful for understanding the genetic basis of XLI in the patients studied, for extending the known mutational spectrum of STS, diagnosis of female carriers and for further application of mutation screening in the genetic counseling of this family.

Klippel-Feil Syndrome With Auxiliary Anterior Cervical Meningomyelocele and Thoracic Syringomyelia: A Case Report.

STUDY DESIGN: Case report. OBJECTIVE: Since this is the first ever case of a male patient with Klippel-Feil syndrome (KFS) with anterior cervical meningomyelocele and syringomyelia. All four previously reported cases were female patients. This makes this case unique. SUMMARY OF BACKGROUND DATA: KFS with auxiliary anterior cervical meningomyelocele is a rare entity. To the best of our knowledge so far only four cases are reported. METHODS: A 22-year-old male patient was presented to neurology outpatient department with 2-year history of left hand paresthesia and progressive weakness. The diagnostic evaluation showed KFS with auxiliary anterior cervical meningomyelocele and thoracic syringomyelia. RESULTS: Patient was sent to neurosurgery department for intervention. After discussing the possible risks and complications of intervention he opted for conservative therapy and declined the surgery. CONCLUSION: The paucity of data is the key reason for any recommended protocol for management of such patients but the available literature recommends neurosurgical intervention in symptomatic patients. LEVEL OF EVIDENCE: 5.

Thymic Stromal Lymphopoietin (TSLP) gene variant rs1837253 is significantly associated with Asthma prevalence in Pakistani Pashtun women.

Asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness and remodeling. Thymic stromal lymphopoietin (TSLP), a member of the interleukin-2 family of cytokines, is produced by activated lung and intestinal epithelial cells, mast, and other immune cells. Population-based studies identified associations between SNPs in the TSLP promoter region and asthma pathogenesis. In this study, we analyzed the genotypic association of TSLP rs1837253 with asthma predisposition in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Target DNA sequence of 250 asthmatics and an equal number of healthy individuals was PCR amplified, and allelic determination was performed by Sanger sequencing. Statistical analysis was conducted using chi-square tests and logistic regression analysis. Homozygous T/T genotype was frequent in the asthmatic subjects with a statistically significant level (P<0.05). Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive were tested while adjusting allele frequencies with covariates (gender and age). Combined C/T and T/T individuals had higher odds ratios of 3.00, 1.91, and 1.73 in co-dominant, dominant, and additive models with statistically significant P-values of 0.029*, 0.022*, and 0.02*, respectively. T allele of rs1837253 was associated with increased susceptibility to asthma among Pashtuns, particularly in females, and we corroborate rs1837253 as a SNP of interest with a potential functional role.

Precisely tailored shell thickness and Ln3+ content to produce multicolor emission from Nd3+-sensitized Gd3+-based core/shell/shell UCNPs through bi-directional energy transfer.

Lanthanide (Ln3+)-doped upconversion nanoparticles (UCNPs) have been paid great attention as multiplexing agents due to their numerous uses in biological and clinical applications such as bioimaging and magnetic resonance imaging (MRI), to name a few. To achieve efficient multicolor emission from UCNPs under single 808 nm excitation and avoid detrimental cross-relaxations between the Ln3+ activator ions (positioned in either the core and/or shell in the core/shell), it is essential to design an adequate nanoparticle architecture. Herein, we demonstrate the tailoring of multicolor upconversion luminescence (UCL) from Nd3+-sensitized Gd3+-based core/shell/shell UCNPs with an architecture represented as NaGdF4:Tm3+(0.75)/Yb3+(40)/Ca2+(7)/Nd3+(1)@NaGdF4:Ca2+(7)/Nd3+(30)@NaGdF4:Yb3+(40)/Ca2+(7)/Nd3+(1)/Er3+(X = 1, 2, 3, 5, 7) [hereafter named CSS (Er3+ = 1, 2, 3, 5 and 7 mol%)]. Such UCNPs can be excited at a single wavelength (∼808 nm) without generation of any local heat. Incorporation of substantial Nd3+-sensitizers with an appropriate concentration in the middle layer allows efficient harvesting of excitation light which migrates bi-directionally across the core/shell interfaces in sync to produce blue emission from Tm3+ (activator) ions in the core as well as green and red emission from Er3+ (activator) ions in the outermost shell. Introduction of Ca2+ lowers the local crystal field symmetry around Ln3+ ions and subsequently affects their intra 4f-4f transition probability, thus enhancing the upconversion efficiency of the UCNPs. By simple and precise control of the shell thickness along with tuning the content of Ln3+ ions in each domain, multicolor UCL can be produced, ranging from blue to white. We envision that our sub-20 nm sized Nd3+-sensitized Gd3+-based UCNPs are not only potential candidates for a variety of multiplexed biological applications (without impediment of any heating effect), but also can act as MRI contrast agents in clinical diagnosis.

Correlation of IL28B rs12979860 genotype and gender with spontaneous clearance of HCV infection: a Pakistani cross-section study.

AIM: There is a strong correlation of IL28B rs12979860 genetic variations and gender with spontaneous clearance of hepatitis C virus (HCV) infection. MATERIALS & METHODS: HCV-infected subjects were categorized into HCV spontaneous clearance (SC) group and chronic hepatitis C (CHC) group on the basis of anti-HCV antibodies and HCV RNA level and follow-up of 6 months. 35 subjects were classified in SC group and 165 subjects were classified in CHC group. IL28B rs12979860 genotypes were determined by allele-specific PCR. RESULTS & CONCLUSION: Multinominal logistic regression analyses revealed that both genders favor IL28B rs12979860 CT genotype (OR: 4.80; CI: 2.22-10.35; p = 0.0005) and (OR: 3.47; CI: 1.63-7.43; p = 0.001) for male and female, respectively, are significant in spontaneous clearance of HCV infection.

Predictive value of IL-28B rs12979860 variants for peg-IFN, sofosbuvir plus ribavirin treatment of HCV infection in Pakistani population.

AIM: The correlation of IL28-B genetic variants (rs12979860) with combinational therapy (peg-interferon, sofosbuvir plus ribavirin) of hepatitis C virus infection were studied in 154 chronic hepatitis C patients. METHODS & RESULTS: The sustained virological response for efficient antiviral regimen was achieved in 75.32% treated individuals. Three genotypes of rs12979860 (CC, CT and TT) were compared both in sustained virological response and nonresponders groups (p = 0.25, p ≤ 0.001, p = 0.10, respectively). CT genotype demonstrated a significant correlation (p ≤ 0.001) in both groups with higher positive predictive value (81.55%). CONCLUSION: IL28 polymorphism and positive predictive value may be considered as the markers for the evaluation of the effectiveness of the treatment regimen. Further clinical trials are recommended to verify the role of IL28-B in hepatitis C virus treatment.

Modern biotechnology-based therapeutic approaches against HIV infection.

The causative agent of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus (HIV). Since its discovery before 30 years, a number of drugs known as highly active antiretroviral therapy have been developed to suppress the life cycle of the virus at different stages. With the current therapeutic approaches, ending AIDS means providing treatment to 35 million individuals living with HIV for the rest of their lives or until a cure is developed. Additionally, therapy is associated with various other challenges such as potential of drug resistance, toxicity and presence of latent viral reservoir. Therefore, it is imperative to search for treatments and to identify new therapeutic approaches against HIV infection to avoid daily intake of drugs. The aim of the current review was to summarize different therapeutic strategies against HIV infection, including stem cell therapy, RNA interference, CRISPR/Cas9 pathways, antibodies, intrabodies and nanotechnology. Silencing RNA against chemokine receptor 5 and other HIV RNAs have been tested and found to elicit homology-based, post-transcriptional silencing. The CRISPR/Cas9 is a gene editing technology that produces a double-stranded nick in the virus DNA, which is repaired by the host machinery either by non-homology end joining mechanism or via homology recombination leading to insertion, deletion mutation which further leads to frame shift mutation and non-functional products. Intrabodies are intracellular-expressed antibodies that are directed towards the targets inside the cell unlike the naturally expressed antibodies which target outside the cell. Different nanotechnology-based therapeutic approaches are also in progress against HIV. HIV eradication is not feasible without deploying a cure or vaccine alongside the treatment.