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Breast cancer is the commonest cancer among females and has a high propensity to metastasize, but gynaecological organs are rarely affected. We report a case where invasive ductal carcinoma of the breast metastasized to the uterus after initial management with curative intent. Our patient was on tamoxifen, which can cause endometrial hyperplasia and lead to a challenge in eventual diagnosis.

Background Xeroderma pigmentosum (XP) is a rare recessively inherited disorder that presents clinical and genetic heterogeneity. Mutations in eight genes, of which seven are involved in nucleotide excision repair (NER) pathway have been reported to cause the XP. Methods and Results Three large consanguineous families of Pakistani origin displaying typical clinical hallmarks of XP were evaluated at clinical and molecular level. Homozygosity mapping using microsatellite markers established linkage of the families to XPC gene on chromosome 3p25.1. Sanger sequencing of the XPC gene identified a novel homozygous single bp deletion [NM_004628.5; c.1934del; p.(Pro645Leufs*5)] and two previously reported mutations that included a nonsense [c.1243 C>T; p.(Arg415*)] and a splice acceptor site (c.2251–1 G>C), all segregating with the disease phenotypes in the families. Conclusion This report has extended the spectrum of mutations in the XPC gene and will also facilitate in diagnosis of XP and counselling of families inheriting it, which is the only inevitable tool for preventing the disease occurrence in future generations.

Breast cancer patients use numerous medications, which include cytotoxic chemotherapy drugs, hormonal agents and supportive medication, so they are more vulnerable to potential adverse drug interactions. This study aimed to evaluate frequency, severity, clinical importance and risk factors responsible for the Drug-drug interactions (DDIs) in a cohort of patients suffering from breast cancer. Data was obtained from 150 patients in the oncology ward (both inpatient and outpatient) with a confirmed diagnosis of breast cancer and currently receiving standard breast cancer-directed treatment. The data was recorded into a pre-designed form specifically made for this study through individual patient interviews and by reviewing the detailed medical chart records of the patients. DDIs were identified by using drug interaction software such as Medscape mobile application and Micromedex version 2. The results of this study showed that all patients were female. The mean numbers of drugs that patients used were 7. Potential drug interactions were identified in 92% of the patients. When drug groups were overviewed, 32% of interactions were between anti neoplastic drugs, 62.9% interactions were between the anti neoplastic agent and supportive care drugs and 5% of them were between anti-cancer drugs and drugs used to treat comorbidities. Major DDIs were found in 62.2% of patients, 25.3% of DDIs were moderate and 12.4% were minor. The number of drugs, comorbid diseases, and selection of chemo protocols were the risk factors for drug interactions. Most of the DDIs found in breast cancer therapy may have adverse consequences on patient health and therapeutic outcomes. Therefore, health care professionals should review the medication regimen of patients with breast cancer before starting any chemotherapy treatment.

Aims: Split-hand/split-foot malformation (SHFM) is a developmental and congenital limb malformation characterized by variable degrees of medial clefting or absence of one or more digits in hands and/or feet. The aim of this study was to identify the underlying cause of three consanguineous Pakistani families showing various types of SHFM-related features. Materials and Methods: Standard molecular methods, including whole-genome sequencing (WGS), whole-exome sequencing (WES), microsatellite markers-based genotyping, and Sanger sequencing were performed to search for the likely causative variants. Results: In family A, WES revealed a novel homozygous missense variant [c.338G>A, p.(Gly113Asp)] in the WNT10B gene. In family B, microsatellite-based genotyping followed by Sanger sequencing revealed a novel homozygous 13 base pairs deletion [c.884-896delTCCAGCCCCGTCT, p.(Phe295Cysfs*87)] in the same gene. In family C, WGS divulged a previously reported heterozygous missense variant [c.956G>A, p.(Arg319His)] in the TP63 gene. Conclusions: Mapping and sequencing genes and variants for severe skeletal disorders, such as SHRM, will facilitate establishing specific genotype-phenotype correlations and providing genetic counseling for the families suffering from such conditions.

Hypohidrotic ectodermal dysplasia (HED) is a congenital anomaly characterized by hypohydrosis, hypotrichosis and hypodontia. Mutations in at least four genes (EDAR, EDARADD, WNT10A, TRAF6) have been reported to cause both autosomal recessive and autosomal dominant forms of HED. Mutations in two other genes (EDA and IKBKG) have been reported to cause X-linked HED. To clinically characterize three consanguineous families (A-C) segregating with autosomal recessive HED and identify possible disease-causing variants of EDAR and EDARADD genes. The genes, EDAR and EDARADD, were sequenced in Family A and C, and exome sequencing was performed in Family B. Additionally, in Family A and C, the effect of the identified variants was examined by analysis of EDAR mRNA, extracted from hair follicles from both affected and unaffected members. Sequence analysis revealed three possible disease-causing EDAR variants including a novel splice acceptor site variant (IVS3-1G > A) in Family A and two previously reported mutations (p.[Ala26Val], p.[Arg25*]) in the two other families. Previously, the nonsense variant p.(Arg25*) was reported only in the heterozygous state. Analysis of the RNA, extracted from hair follicles, revealed skipping of a downstream exon in EDAR and complete degradation of EDAR mRNA in affected members in family A and C, respectively. Computational modelling validated the pathogenic effect of the two variants identified in Family B and C. The three variants reported here expand the spectrum of EDAR mutations associated with HED which may further facilitate genetic counselling of families segregating with similar disorders in the Pakistani population.

Background: Frontonasal dysplasia (FND) is a rare developmental disorder characterized by mild to severe changes in skull and brain structures. It is a phenotypically variable and heterogeneous disorder. This study was designed to provide a clinical and genetic analysis of FND in a consanguineous family of Pakistani origin. Methodology and Results: Affected individuals in the family showed characteristic features of frontonasal dysplasia type-2 (FND2), such as nasal bone hypoplasia, hypertelorism, and alopecia. Skull and brain imaging of affected members revealed ossification defects and various types of brain structural anomalies that created a split-brain. Sanger sequencing of the ALX4 gene revealed a homozygous missense variant [NM_021926.4: c.652C>T; p.(Arg218Trp)] in three affected members who demonstrated severe craniofacial anomalies. Heterozygous carriers in the family showed mild FND2 phenotypes. Conclusion: Clinical and genetic analysis of a family, exhibiting FND2 phenotypes, revealed several previously unreported clinical features and a novel missense variant in the ALX4 gene. These results will facilitate diagnosis and genetic counseling of the FND patients in the Pakistani population.

Polycystic ovary syndrome (PCOS) is an oligogenic condition characterised by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Previously, European and Han Chinese populations identified different susceptibility loci, of which ERBB4 (rs1351592) was strongly associated with PCOS. Our study aimed to investigate the association of ERBB4 Single Nucleotide Polymorphism (SNP), rs1351592 with PCOS in Pakistani women of Hazara region. Fifty PCOS patients and 14 healthy women were recruited and SNP was replicated using ARMS-PCR and sequencing. The study showed that Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH), and Testosterone (T) were significantly elevated in patients compared to controls (P0.05). Overall, the frequency of G allele was higher than C allele and the SNP lacked significant association with PCOS. This is the first study demonstrating the association of ERBB4 SNP, rs1351592 with PCOS in Pakistani population. Further research using larger population size will help to estimate the role of ERBB4 SNP as potential biomarker for disease diagnosis.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade, malignant fibroblastic tumor. Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by dysregulated production of granulocytic cell line without the loss of their capacity to differentiate. To our knowledge, there is no described association of DFSP with CML in literature. The authors have encountered a first case of DFSP coexisting with chronic myeloid leukemia.

Background: The syndromic and non-syndromic congenital missing teeth phenotype is termed tooth agenesis. Since tooth agenesis is a heterogeneous disorder hence, the patients show diverse absent teeth phenotypes. Thus identifying novel genes involved in the morphogenesis of ectodermal appendages, including teeth, paves the way for establishing signaling pathways.Methods and Results: We have recruited an autosomal recessive non-syndromic tooth agenesis family with two affected members. The exome sequencing technology identified a novel missense sequence variant c.1421T > C; p.(Ile474Thr) in a regulatory factor X (RFX) family member (RFX2, OMIM: 142,765). During the data analysis eight rare variants on various chromosomal locations were identified, but the co-segregation analysis using Sanger sequencing confirmed the segregation of only two variants RFX2: c.1421T > C; p.(Ile474Thr), DOHH: c.109C > G; p.(Pro37Ala) lying in a common 7.1 MB region of homozygosity on chromosome 19p13.3. Furthermore, the online protein prediction algorithms and protein modeling analysis verified the RFX2 variant as a damaging genetic alteration and ACMG pathogenicity criteria classified it as likely pathogenic. On the other hand, the DOHH variant showed benign outcomes.Conclusion:RFX2 regulates the Hedgehog and fibroblast growth factor signaling pathways, which are involved in the epithelial and mesenchymal interactions during tooth development. Prior animal model studies have confirmed the expression of rfx2 at a developmental stage governing mouth formation. Moreover, its regulatory role and close association with ciliary and non-ciliary genes causing various dental malformations makes it a potential candidate gene for tooth agenesis phenotype. Further studies will contribute to exploring the direct role of RFX2 in human tooth development.

Green nanotechnology-based approaches have been acquired as environmentally friendly and cost effective with many biomedical applications. The present study reports the synthesis of silver nanoparticles (AgNPs) from the leaves of

Aim: To determine the relationship between serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and active disease in patients with juvenile rheumatoid arthritis (JRA). Methods: This is a cross-sectional analytical study conducted over a year from October 2020 to October 2021 at Lady Reading Hospital, Peshawar Rheumatology and Pediatrics Unit. All MJA patients who met the criteria of the American College of Rheumatology (ACR) were enrolled in the study. The ACR 20 recovery criteria were used to define disease forgiveness, and those meeting the ACR 20 recovery criteria were included in the remission group. Laboratory tests such as PCR and ESR were done. Statistical analysis was performed using SAS software (version 10.3). Results: 90 patients were enrolled in the study, 28 (31.2%) in the remission group and 62 (68.88%) in the active disease group. There were 61.11% (n = 55) of women, and the ratio of men to women was 3: 4. The mean age of the subjects was 10.12 ± 3.39 years (4-17 years). Age distribution at reporting by different subgroups, 13 patients (14.44%) 1-5 years old, 31 patients (34.44%) 5-10 years old, 40 patients 10-15 years old (44.44 %), and 6 patients (6.66) were over 15 years of age. The mean disease duration was 2.40 + 2.11 years (range = 0.3 to 7 years). The onset of the disease in 21 patients (23.33%) was after one year (22.9%), in 48 patients (53.33%) between years and 5 years from the onset of the disease, in 21 patients (23.33%) five years. The most common type of arthritis was polyarthritis in 43 patients (47.77%), followed by polyarthritis in 31 patients (34.44%), and systemic onset in 12 patients (13.33%). The mean ESR was 41.03 + 27.80 mm / h 1 (range = 07-128 mm / h 1) and the mean CRP was 16.1 + 13.80 mg / L (range = 6-47 mg / L). ESR was> 30 mm / 1 hour. in 50 (55.55%) of 90 patients, while 43 (86%) of these 50 patients were in the active disease group. Similarly positive CRP was detected in 58 (64.44%) patients, of which 52 (89.7%) belonged to the group with active disease. Compared to the remission and active disease groups, 33 of the patients with active disease were female. In the active disease group, the mean age was 11.01 + 3.30 years, and the duration of the disease in patients started after one year. Polyarthritis was detected in 26/62 (41.9%) of patients from the active group of the disease. Conclusions: High CRP and ESR parameters are good in predicting active disease in JRA patients. Key words: C-reactive protein, juvenile rheumatoid arthritis, JRA and erythrocyte activity.

Breast cancer is the most frequent cancer in women and has a high proclivity for metastasizing, yet it seldom affects gynaecological organs. We present a case of invasive ductal carcinoma of the breast that metastasized to the uterus following initial curative treatment. Our patient was taking tamoxifen, which can induce endometrial hyperplasia and make diagnosis more complicated.

Lafora body disease (MIM-254780), a glycogen storage disease, characterized by Lafora bodies (deformed glycogen molecules) accumulating in multiple organs, is a rare form of myoclonic epilepsy. It manifests in early adolescent years, initially with seizures and myoclonus, followed by dementia and progressive cognitive decline, ultimately culminating in death within 10 years. In Pakistan so far 5 cases have been reported. Here, we report a new case of Lafora body disease belonging to a consanguineous family from Pakistan. Histopathological analysis confirmed presence of lafora bodies in the patient`s skin. Sanger sequencing revealed novel homozygous 5bp deletion mutation (NM_005670.4; c.359_363delGTGTG) in exon 2 of the EPM2A gene, which was truly segregated in the family. These results will increase our understanding regarding the aetiology of this disorder and will further add to the mutation spectrum of EPM2A gene.

Rhabdomyosarcoma is a malignancy of mesenchymal tissue origin typically occurring in childhood and adolescence, with an incidence rate of of 4.3 patients per million population per anum. Primary rhabdomyosarcoma of para-testicular origin is an infrequent condition, making up to 7% of all the cases of rhabdomyosarcoma tumors in children and adolescents. Here we describe a case of a 25 years old man with left paratesticular solid mass. He underwent left sided orchiectomy with histopathology revealing paratesticuler embryonal rhabdomyosarcoma. He underwent definitive chemo-radiotherapy and orchidopexy with complete remission and is on active surveillance for 4 years.

BACKGROUND: This study was conducted to analyze the effects of endophytic Bacillus megaterium (BM 18‐2) colonization on structure strengthening, microbial community, chemical composition and stabilization properties of Hybrid Pennisetum. RESULTS: The BM 18‐2 had successfully colonized in the interior tissues in both leaf and stem of Hybrid Pennisetum. During ensiling, the levels of pH, acetic acid (AA), butyric acid (BA), propionic acid (PA), and the population of yeast and aerobic bacteria were significantly (P > 0.05) lower, while lactic acid bacteria (LAB) and lactic acid (LA) were significantly (P

This study explored the antibacterial efficacy of Pistacia integerrima gall, leaf and bark in different solvents. Extracts of these parts prepared in ethanol, methanol and distilled water by using rotary evaporator. To check the antibacterial potential of this plant, minimal inhibitory concentrations of each extract analysed by agar well diffusion method against Staphylococcus aureus, E. coli, Proteus vulgaris, Bacillus subtilis and Pseudomonas aeruginosa. For anticancer activity, hexane, chloroform and ethyl acetate fractions of P. integerrima gall, leaf and bark used against human cervical cancer (HeLa) and baby hamster kidney (BHK–21) cell lines. Results showed that maximum zone of inhibition 25mm formed with ethanolic gall extract in 200µL concentration against B. subtilis. P. vulgaris shows resistance to methanol and aqueous extracts but inhibited with ethanolic leaf extract. Among different parts of P. integerrima, n-hexane leaf fraction shown to be most effective against HeLa cell lines with IC50 of 7.45 µg/mL. In case of BHK-21, highest cell inhibition of 46.8% observed with crude leaf extract than ethyl-acetate bark extract (44.9%) of P. integerrima. It is concluded that the effective inhibitor was hexane leaf fraction against HeLa cell lines in which Heneicosane was found (39.7%) which might be responsible for anticancer activity.

Background- The typical definition of fatigue is the feeling of aversion to effort, lack of energy, weariness, and early exhaustion. Due to inactive lifestyle, the rate of fatality became after three years of stroke in individuals who are the survivor of stroke with fatality. The induced activity which damage the ability to exert force is called Neuromuscular fatigue. Neuromuscular fatigue can be measured by the reduction in ability of muscles for exerting a force during an activity. After stroke, the walking function greatly impacted by the paretic leg muscles fatigue. That’s why, muscular fatigue in people after stroke can be quantitatively measured by the association of walking function with paretic leg muscles. This is a slight research which particularly measures the neuromuscular fatigue resulting stroke. The main objective of this study was to access relation of neuromuscular fatigue which can result in stroke and compare it with gender and age matched healthy individuals. Methodology- For this study total 80 subject were taken, and by purposive sampling these 80 participants divided in to two groups named as control group and experimental group and each group had 40 subjects. All those patients were included who were diagnosed to have chronic stroke before six months by Registered Doctors. Using Dual Bio Stimulator/Amp the hamstrings and quadriceps muscles activity of all subject were recorded of both non-paretic and paretic side. By performing “Maximum Voluntary Contraction” (MVC) exercise EMG signals induced in Pre-fatigue were recorded on both muscles of all participants. Also, in the same way “Sit to Stand test (STS)” was performed on all patients and exercise EMG signals were recorded induced in post-fatigue. To assess the chronic fatigue “Fatigue Severity Scale (FSS)” was used whereas to assess the subjective levels of pre and post exercise in fatigue “Visual Analog Fatigue Scale (VAFS)” was used. Results- “In hamstrings the mean activity of post fatigue EMG is significantly lower as compared to the mean activity of pre-fatigue EMG in non-paretic, paretic and control study group. Likewise, in quadriceps, the mean activity of post fatigue EMG is significantly lower as compared to the mean activity of pre-fatigue EMG in non-paretic, paretic and control study group.” Conclusion- In this study it was observed that in chronic stroke, the peripheral neuromuscular fatigue is different in comparison of matched control group with same gender and age. Keywords: Visual analog fatigue scale, Fatigue severity scale, Surface electromyography, neuromuscular fatigue, Chronic stroke, Chronic fatigue.

Objective- In newborn infant’s pain management is underused particularly for mild to moderate pain. For this purpose, glucose and sucrose use can be very effective. The main objective of this is to analyze the oral dextrose effects on pain relief in newborn infants. Methodology- For this study 124 newborn infants were enrolled for clinical trial which was randomized controlled. The Study was conducted in Bahawalpur Victoria Hospital in Paediatric unit .Before venipunctures, the enrolled infants were randomized to get breast milk or oral dextrose (25%) two minutes. After venipunctures, to know the pain reactions oxygen saturation, heart rate, and NIPS pain scoring system was recorded. Results- After venipunctures in dextrose group, pain was significantly lower (at 1st minute NIPS pain score was 6.62+0.82 and 4.67+1.04, at 2nd minutes it was 4.08 ± 1.05 and 2.04 ± 1.45 and at 3rd minutes it was 3.02+1.08 and 1.63+0.76 respectively). After comparison it was observed that 1st group heart rate was higher than the 2nd group as in 2nd group it was (144.8 ± 12.44/min) and in 1st group it was (166.57 ± 12.25/min). In both groups, desaturation was observed. Conclusion- In newborn to manage pain from mild to moderate the solution of 2ml of 25% dextrose is non-pharmacologic, non-expensive, easy, and useful method. Keywords: analgesia, breast milk, dextrose, newborn, pain.

Non-syndromic oculocutaneous albinism (nsOCA) is an inherited disorder of melanin biosynthesis with autosomal recessive mode of inheritance, presenting either hypopigmented or depigmented skin, hair, and eyes. It is genetically heterogeneous with seven loci (OCA1–OCA7) reported to date. In the present study, we have reported three consanguineous families (A, B, C) presenting identical nsOCA phenotypes. Sanger sequencing revealed a novel [NM_000372.5: c.826 T > C, p.(Cys276Arg)] and a recurrent variant [NM_000372.5: c.832C > T, p.(Arg278∗)] in tyrosinase (TYR) in families A and B, respectively. Microsatellite marker-based homozygosity mapping linked family C to OCA4. Sequence analysis identified a novel insertion variant (NM_016180.5: c.1331_1332insA) in the SLC45A2. Further, in silico mutagenesis and dynamic simulation approaches revealed that a novel Cys276Arg variant abolished the cysteine bridge and might contribute toward decreased stability of the TYR protein. Our study expands the mutation spectrum of the TYR and SLC45A2 genes and emphasizes that molecular investigations are essential for accurate disease diagnosis.

Breakdown of the crude oil contaminant by soil microbial community in the bioremediation can be enhanced in the presence of plant rhizosphere, but plant cannot grow and tolerate the high concentration of hydrocarbon. Composting of the crude oil-contaminated soil was found to be an effective technology to decrease the pollutant concentration to the acceptable level for plant growth. Phytoremediation with native plants followed with composting can be performed well, but the microbial abundance in the contaminated soil usually becomes much low as time passes. In order to enhance the degradation potential of heterotrophic microorganisms in bioremediation, different bioaugmentation techniques are used, while few researches also used plant rhizosphere along with it, but the results are ambiguous. The present chapter will explore this ambiguity by providing the complete description about the bioremediation and the facts that plant rhizosphere selects microbial community, which is more suitable for pollutant degradation than addition of microbial culture in soil. Rhizodegradation followed with composting is found to be a useful treatment method for extremely polluted soil, and bioaugmentation with immobilized and free bacterial culture was found more effective without plant.

The aim of the current study was to evaluate the effect of dietary supplementation of Pinus ponderosa leaves (pine leaves) and α-tocopherol acetate (vitamin E) powder on male reproductive system, serum metabolites and carcass characteristics of Japanese quails. A total of 360-day-old male quails were purchased from the open market and kept at poultry shed for ninety-four days. After ten days of adaptation, all quails were randomly assigned into 4 groups, control (IC); supplemented with α-tocopherol acetate (IE) at the rate of 150 mg/L; Pinus ponderosa leaves (IP) at the rate of 150 mg/L; and 70 mg α-tocopherol acetate and 70 mg Pinus ponderosa leaves (IEP). Pinus ponderosa leaves and α-tocopherol acetate supplementation had not significantly (p .05) effected on final body weight gain, feed intake and feed conversion ratio of quails. The high-density lipoprotein cholesterol (HDLC) and total cholesterol (TC) were significantly (p .05) affected by IE and IP groups as compared to IC and IEP groups. Triglyceride (TG), glutathione peroxidase (GPx) and superoxide dismutase (SOD) significantly (p .05) increased in all treatment groups except for the IC group. Aspartate transaminase (AST) significantly (p .05) decreased in treatment groups as compared to control group. Overall, the mineral levels significantly (p .05) increased in treatment groups as compared to control. Cloacal gland index values, the quantity of foam production and testis weight were significantly (p .05) increased in treatment groups. It was concluded that the supplementation of Pinus ponderosa leaves and α-tocopherol acetate improved the testis weight, foam production, serum antioxidant enzymes and mineral level especially zinc in Japanese quail considered an indicative characteristic of higher sperm production rate and improved sexual activity. Further, higher gametogenesis rate, sperm production or reproductive behaviour including different hormonal level will be analysed in future study.

Frontonasal dysplasia (FND) is a heterogeneous group of disorders characterized by hypertelorism, telecanthus, broad nasal root, wide prominent nasal bridge, short and wide nasal ridge, broad columella and smooth philtrum. To date one X-linked and three autosomal recessive forms of FND have been reported in different ethnic groups. We sought to identify the gene responsible for FND in a consanguineous Pakistani family segregating the disorder in autosomal recessive pattern. Genome-wide homozygosity mapping using 250KNsp array revealed five homozygous regions in the selected affected individuals. Exome sequencing found a novel splice acceptor site variant (c.661-1G>C: NM_006982.2) in ALX1. Sanger sequencing confirmed the correct segregation of the pathogenic variant in the whole family. Our study concludes that the splice site variant identified in the ALX1 gene causes mild form of FND.