The association of ABCB1 gene polymorphism with clinical response to carbamazepine monotherapy in patients with epilepsy.

BACKGROUND: Epilepsy is a common neurological disease but around 30% of patients fail to respond to antiepileptic drug (AED) treatment. Genetic variation of the ATP-binding cassette subfamily B, member 1 (ABCB1) gene, a drug efflux transporter may infer treatment resistance by decreasing gastrointestinal absorption and preventing AED entry into the brain. This study examined the impact of ABCB1 genetic variants on carbamazepine responsiveness. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of 104 epileptic patients. Genotyping of 3 ABCB1 variants (c.C3435T, c.G2677T/A and c.C1236T) was undertaken using validated TaqMan allelic discrimination assays. Plasma carbamazepine levels were measured at 3 and 6 months following the initial dose using high-performance liquid chromatography (HPLC) alongside clinical outcomes evaluation. RESULTS: Nonresponse to carbamazepine (CBZ) was associated significantly with the ABCB1 variants c.C3435T, c.G2677T/A, c.C1236T and TTT, TTC haplotypes (P < 0.05). There was no significant association between variants and plasma CBZ level (P > 0.05). CONCLUSIONS: Our results showed that variant alleles of the ABCB1 gene and TTT, TTC haplotypes were significantly associated with CBZ resistance without affecting the plasma level of carbamazepine. The findings of this study may help to predict patient's response to treatment ultimately it will improve the personalized and evidence based treatment choice of patients with epilepsy.

Conservation and upgradation of indigenous Cholistani cattle breed of Pakistan: a pathway to sustainable livestock.

Pakistan is endowed with many established indigenous zebu Bos indicus type (humped) cattle breeds including Sahiwal, Red Sindhi, Bhagnari and Cholistani. Amongst these indigenous cattle breeds, Sahiwal and Red Sindhi have extensively been navigated and hence these two are acclaimed as internationally recognized breeds. However, research work on Cholistani cattle breed actually initiated in 2010 and has attained a steady pace. This breed was a new entrant in Livestock Census of Pakistan since 2006. Cholistani is a hardy, tick-resistant, adaptable cattle breed being reared under pastoral nomadism of the Cholistan desert, Pakistan. The present narrative review is the first of its kind intended to sum-up all the research work conducted about this indigenous cattle breed, and to put forth research gaps for this formerly neglected cattle breed. The review discusses the research work conducted on Cholistani cattle breed under five major research subjects/domains i.e. production attributes, theriogenology-related attributes, hematochemical attributes, disease, epidemiologic and therapeutic attributes, and genetic attributes. Future horizon for research avenues has also been given. It is the dire need of time that specific breed-oriented conservation and propagation programs may be initiated in the country so that sustained livestock and enhance socioeconomic profiling of rural communities may be attained.

Rosmarinic acid alleviates ultraviolet-mediated skin aging via attenuation of mitochondrial and ER stress responses.

Chronic exposure to Ultraviolet B radiation (UV-B) evokes a myriad of toxic signalling events in the irradiated skin. One of such response is ER stress, which is known to exacerbate photodamage responses. Also, recent literature has highlighted the adverse impact of environmental toxicants on mitochondrial dynamics and mitophagy. Impaired mitochondrial dynamics escalates oxidative damage and causes apoptosis. There have been evidences that support crosstalk between ER stress and mitochondrial dysfunction. However, mechanistic clarification is still needed to verify the interactions between UPR responses and mitochondrial dynamics impairment in UV-B-induced photodamage models. Lastly, plant-based natural agents have garnered attention as therapeutic agents against skin photodamage. Thus, gaining mechanistic insights of plant-based natural agents is required for their application and feasibility in clinical settings. With this aim in view, this study was performed in primary human dermal fibroblasts (HDFs) and Balb/C mice. Different parameters regarding mitochondrial dynamics, ER stress, intracellular damage and histological damage were analyzed using western blot, rt-PCR and microscopy. We demonstrated that UV-B exposure leads to induction of UPR responses, upregulation of Drp-1 and inhibition of mitophagy. Further, 4-PBA treatment leads to reversal of these noxious stimuli in irradiated HDF cells, thereby, indicating an upstream role of UPR induction in mitophagy inhibition. Also, we explored the therapeutic effect of Rosmarinic acid (RA) against ER stress and impaired mitophagy in photodamage models. RA prevents intracellular damage via alleviation of ER stress and mitophagic responses in HDFs and irradiated Balb/C mice skin. The current study summarizes the mechanistic insights into UVB-mediated intracellular damage and role of natural plant-based agent (RA) in ameliorating these toxic responses.

Insights into metabolic and pharmacological profiling of Aspergillus ficuum through bioinformatics and experimental techniques.

BACKGROUND: Recently, numerous novel bioactive fungal metabolites have been identified that possess broad therapeutic activities including anti-inflammatory, antibiotic, antioxidant, and antitumor. The fungal mycochemicals as well as extracts have increased the interest of the scientific community in drug discovery research through a combination approach such as, molecular metabolic, pharmacological and computational techniques. Therefore, the natural fungus Aspergillus ficuum (A. ficuum) (FCBP-DNA-1266) was selected for metabolic and pharmacological profiling in this study. RESULTS: The metabolic profile of A. ficuum was explored for the first time and revealed the presence of bioactive compounds such as choline sulfate, noruron, hydroxyvittatine, aurasperone D, cetrimonium, kurilensoside, heneicosane, nonadecane and eicosane. Similarly, a pharmacological screen of A. ficuum was performed for the first time in in vivo and in vitro models. Interestingly, both the ethyl acetate and n-hexane fractions of A. ficuum were found to be more active against Bacillus subtilis among five tested bacteria with their zone of inhibition (ZOI) values of 21.00 mm ±1.00 and 23.00 mm ±1.00, at a concentration of 150 µgmL-1 respectively. Similarly, a significant decrease (P<0.001) and (P<0.01) in paw edema was observed in A. ficuum-treated animals at doses of 50 and 150 mgkg-1, respectively, reflecting its potent anti-inflammatory effect. Furthermore, the docking results supported the antibacterial and anti-inflammatory effects of A. ficuum. In addition, the crude extract demonstrated no acute toxicity and the highest percent radical scavenging was recorded for both n-hexane and ethyl acetate extracts. CONCLUSION: The metabolic profile of A. ficuum indicated the presence of biological relevant compounds. A. ficuum extract exhibited potent antibacterial and anti-inflammatory effects supported by docking results. Furthermore, A. ficuum extract demonstrated the highest percentage of radical scavenging activity along with no acute toxicity.

Molecular docking and dynamic simulations of Cefixime, Etoposide and Nebrodenside A against the pathogenic proteins of SARS-CoV-2.

The catastrophe of the coronavirus continues from one part of the world to another, and hardly a country is left without its devastations. Millions of people were infected and several hundred thousand died of the COVID-19 pandemic across the world. There is no clear targeted drug therapy available for the treatment of the patients. The discovery of vaccines is not enough to curtail its spread and disastrous implications. An instantly qualifying approach is needed to utilize the current drugs and isolated compounds. The purpose of this work is to determine potent inhibitors against the target proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, molecular docking study of pathogenic spike glycoproteins (S), nucleocapsid phosphoprotein (N), an envelope protein (E), two drugs i.e., cefixime, etoposide, and a previously isolated compound nebrodenside A is performed. Promising results were obtained via complimentary analysis of molecular dynamics (MD) simulations performed for the complexes of three proteins with etoposide drug. Minimum values were recorded for the docking scores and binding energies of the complexes. These results were further supported by the RMSD, RMSF data for the stability of proteins and ligands. Additionally, ligand properties and ligand-protein contacts were also explained with histograms of every simulation trajectory. The computational studies confirmed that cefixime, etoposide, and nebrodenoside A can be used as potent inhibitors of COVID-19. Nevertheless, additional experimental investigations and validation of the selected candidates are mandatory to confirm their applicability for clinical trials.

Cutaneous Leishmaniasis in Pakistan: a neglected disease needing one health strategy.

BACKGROUND: Cutaneous Leishmaniasis (CL) is a neglected tropical disease, which mainly affects poor communities. It is one of the major vector-borne disease and endemic in Pakistan. METHODS: A case-control study to evaluate potential risk factors of human-CL was conducted in Khewra region, District Jhelum, Pakistan from January-April 2014. Case data about 90 cases registered during October 2012 to November 2013 was retrieved from Municipal Hospital. Controls were matched (1,1 ratio) on the date of registration with cases from same hospital. Both cases and controls were invited to participate and data was collected in a face-to-face interview. A prospective study of canine leishmaniasis (canine-CL) was also conducted at Civil Veterinary Hospital in the same area. Suspected dogs with skin ulceration signs were included in the study and blood samples were collected. Statistical analyses were conducted to determine association between various parameters and outcome of interest. RESULTS: The ages of cases ranged from 1 to 76 years (median = 15 years) and proved to be protective factor i.e. increase in each year in age reduced the likelihood of being infected with human-CL [Odds Ratio (OR) = 0.4, 95% Confidence Interval (CI) = 0.25-0.76]. People sleeping outsides in an open area were more likely to become a case (OR = 8.7, 95% CI = 2.90-26.37) than a control. Poor sanitary condition inside the house (OR = 3.3, 95% CI 1.03-10.56) and presence of other animals in house (livestock, poultry) (OR = 3.6, 95% CI = 1.07-12.12) also identified as risk factors of high significance. The proportion of positive dogs with canine-CL was 21.05% and was significantly associated with human-CL cases in the same area (p < 0.05). CONCLUSIONS: We concluded that adopting self-protections measures against sand-fly, and maintaining good hygiene may lower the risk of human-CL. One-Health Strategy is suggested to control leishmaniasis in human and dog population.

Depression in persons with epilepsy: A comparative study of different tools in Indian population.

OBJECTIVE: Depression is an important co-morbidity in persons with epilepsy (PWE) and its timely identification is essential. The aim of the study was to assess and compare the psychometric properties of potentially suitable screening tools of depression in PWE in a tertiary care setting in India. METHODS: After ethical clearance, 449 PWE above 18 years of age, on anti-seizure drugs (ASDs), attending epilepsy clinic in neurology outpatient department (OPD) of All India Institute of Medical Sciences, New Delhi, India, were recruited and evaluated for depression using different tools namely: Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Patient Health Questionnaire (PHQ-9) and Hamilton Depression Rating Scale (HAM-D). Mini International Neuropsychiatric Interview (MINI: Module A, version 6.0.0) was used as reference standard. The association if any of depression with PWE variables was also determined. RESULTS: A variable percentage of PWE were positive for depression- 40.1% with MINI, 40.5% with NDDI-E, 44.3% with HAM-D and 45.4% with PHQ-9. Suicidal ideation was present in 4.5% of PWE. The sensitivity and specificity of scales using MINI as a reference standard were found to be maximal at scores ≥5, ≥8 and >11 for PHQ-9, HAM-D, and NDDI-E, respectively. The ROC analysis revealed a statistically significant difference among NDDI-E and PHQ-9 (p = 0.0268). Polytherapy in PWE had significant association with risk of depression (p < 0.01) and female PWE had 1.5 times the odds of depression as compared with males (95% CI, 1.02-2.2). CONCLUSION: All the tools used in this study were found to be appropriate for use in PWE if cut-off points are validated. The choice of tool can be based on the clinical setting.

Prevalence of depression and suicidal ideation in persons with epilepsy during the COVID-19 pandemic: A longitudinal study from India.

OBJECTIVES: COVID-19 pandemic has disrupted healthcare services for chronic disorders such as epilepsy. In this study, the impact of COVID-19 pandemic on persons with epilepsy (PWE) with regard to their seizure control, depression status, and medication adherence was assessed. METHODS: After ethical clearance, 449 PWE who had been previously evaluated for depression at All India Institute of Medical Sciences (AIIMS), New Delhi, India, were telephonically revaluated using Mini International Neuropsychiatric Interview and surveyed for source of medication and medication adherence over past 6 months. The prevalence and the association of depression, suicidality, and seizures during pandemic with different PWE variables were determined. RESULTS: Out of 449 PWE, 70.6% responded. 19.9% were diagnosed positive for depression as per MINI while suicidal ideation was observed in 5.4%. Seventy six (23.9%) PWE reported seizures during pandemic. The incidence was greater in females, unemployed, previously uncontrolled epilepsy, polytherapy, altered use of medications, and depressed PWE. Seizure during pandemic, increased seizure frequency, previous history of depression, and altered use of medications were all significantly associated with depression during COVID-19 pandemic (2.6-95%CI, 1.45-4.73; 1.9-95%CI, 1.01-3.57; 8.8-95%CI, 4.54-17.21; 2.9-95%CI, 1.19-7.24), and polytherapy (2.9-95%CI, 0.92-9.04), seizures during pandemic (3.9-95%CI, 1.45-10.53) and previous history of depression and suicidality, were related with suicidal ideation. CONCLUSION: COVID-19 pandemic-induced disruptions can be detrimental for PWE, and restoring services to the precovid levels as well as putting appropriate continuity plans in place for care of PWE should be a priority.

Point prevalence of depression in persons with active epilepsy and impact of methodological moderators: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to determine the pooled prevalence of depression in persons with epilepsy and assess the methodological moderators affecting the prevalence estimates. METHODS: Five electronic databases PubMed, The Cochrane Library, EMBASE, WHO Global Index Medicus, and Clinicaltrial.gov were searched for studies reporting prevalence of depression in PWE ≥ 18 years of age in any setting. RESULTS: Out of 13,873 studies, after deduplication and screening, 56 studies with 10,527 PWE met the eligibility criteria. The overall pooled prevalence of depression in PWE was 32% (95%confidence interval [CI] 28-35%) and significant heterogeneity (Chi-square = 1171.53, p = 0.00; τ2 = 0.02; I2 = 94.36%). Prevalence has doubled in the recent years (16% in 2000-2005 vs. 35% in 2016-2020), was higher in Asia than in Europe (coefficient 0.899, 95%CI: 0.809-0.999; p = 0.049). Among assessment methods, prevalence was highest in HAM-D scale (54%, 95%CI: 27-82%) and lowest in MINI (22%, 95%CI: 19-26%). Sensitivity analysis also corroborated findings when MINI was excluded (35%, 95%CI: 31-38%). CONCLUSIONS: A significant proportion of PWE have depression. Though there is substantial heterogeneity due to various methodological moderators, it is unlikely to affect the routine screening of PWE for depression. Use of a screening tool should be based on ease of administration, and cutoff selection should ensure identification of minimal depression as well.

Fabrication of a carbon nanotube/tungsten disulfide visible spectrum photodetector.

Two-dimensional-material-based photodetectors are gaining prominence in optoelectronic applications, but there are certain factors to consider with bulk material usage. The demand for a highly responsive and highly efficient device with an inexpensive fabrication method is always of paramount importance. Carbon nanotubes (CNT) are well known, owing to their upheld vigorous structural and optoelectronic characteristics, but to fabricate them at a large scale involves multifarious processes. A visible range photodetector device structure developed using a simple and inexpensive drop-casting technique is reported here. The optoelectronic characteristics of the device are studied with IV measurements under the light and dark conditions by incorporating a thin CNT layer on top of tungsten-disulfide-based heterojunction photodetector to enhance the overall characteristics such as detectivity, responsivity, photocurrent, rise time, and fall time in the visible range of the light spectrum with a violet light source at 441 nm. In the DC bias voltage range of -20 to 20 V, IV measurements are carried out under dark and illumination conditions with different incident power densities. The threshold voltage is recognized at 2.0 V. Photocurrent is found to be highly dependent on the state of the incident light. For 0.3074mW/cm2 illuminated power, the highest responsivity and detectivity are determined to be 0.57 A/W and 2.89×1011 Jones. These findings encourage an alternative fabrication method at a large scale to grow CNTs for the enhancement of optoelectronic properties of present two-dimensional-material-based optoelectronic and photonics applications.

Management of sport-related concussion in emergency departments in England: a multi-center study.

OBJECTIVE: To establish the current knowledge of sport-related concussion (SRC) management of clinicians in emergency departments in the North West of England. METHODS: A cross-sectional, multi-center study design was used and included emergency department clinicians (EDCs) across 15 centers in the North West of England. A 22-question survey was issued with questions focused on the 5th International Conference on Concussion Consensus Statement. Absolute and percentages were presented, and comparisons in knowledge of guidelines and confidence between EDCs were made using the Kruskal-Wallis test. RESULTS: Of an estimated 300 EDCs, 111 (37%) responded. Thirty (27%) were aware of the guidelines, whilst 63 (57%) had heard of a graduated return-to-sport protocol. Physical rest was advised by 106 (95%) respondents, with 68 (61%) advising cognitive rest and 47 (42%) providing written advice. There was no difference (p > .05) in awareness of SRC guidelines or confidence between clinician grade, with most receiving no SRC training. CONCLUSIONS: There is a lack of knowledge amongst EDCs in the North West of England in managing and providing discharge advice to patients with SRC. This is likely due to the limited awareness of guidelines and training, and therefore further education delivery on SRC management guidelines is required.

Understanding reasons for electing gap years between undergraduate education and medical school and the impact of gap years on the student experience of medical education.

Gap years have grown in popularity among students attempting to go to medical school in recent years. According to the Association of American Medical Colleges (AAMC), more than half of matriculated students now have taken time off between their undergraduate studies and medical school. Although many claim benefits to taking gap years, research on the impacts of these experiences on medical students is largely nonexistent. This study aimed to qualitatively analyze the gap year phenomenon and its impacts on medical students through semistructured interviews conducted at the University of Central Florida College of Medicine. Through these interviews, the research team collected in-depth responses that were thematically analyzed. Analysis revealed the following major themes regarding the impacts of gap years: 1) adaptability to change and failure, 2) professional identity formation and understanding of team role, 3) understanding the "real world," 4) refocusing of goals, 5) resilience and stress management, and 6) reinforcement of motivation.

Taking a step down on the reconstruction ladder for head and neck reconstruction during the COVID-19 pandemic.

BACKGROUND: Most of the head and neck cancers are time-critical and need urgent surgical treatment. Our unit is one of the departments in the region, at the forefront in treating head and neck cancers in Pakistan. We have continued treating these patients in the COVID-19 pandemic with certain modified protocols. The objective of this study is to share our experience and approach towards head and neck reconstruction during the COVID-19 pandemic. RESULTS: There were a total of 31 patients, 20 (64.5%) were males and 11 (35.4%) patients were females. The mean age of patients was 52 years. Patients presented with different pathologies, i.e. Squamous cell carcinoma n = 26 (83.8%), mucoepidermoid carcinoma n = 2 (6.4%), adenoid cystic carcinoma n = 2 (6.4%) and mucormycosis n = 1 (3%). The reconstruction was done with loco-regional flaps like temporalis muscle flap n = 12 (38.7%), Pectoralis major myocutaneous flap n = 8 (25.8%), supraclavicular artery flap n = 10 (32.2%) and combination of fore-head, temporalis major and cheek rotation flaps n = 1 (3%). Defects involved different regions like maxilla n = 11 (35.4%), buccal mucosa n = 6 (19.3%), tongue with floor of mouth n = 6 (19.3%), mandible n = 4 (12.9%), parotid gland, mastoid n = 3 (9.6%) and combination of defects n = 1 (3%). Metal reconstruction plate was used in 3 (9.6%) patients with mandibular defects. All flaps survived, with the maximum follow-up of 8 months and minimum follow-up of 6 months. CONCLUSION: Pedicled flaps are proving as the workhorse for head and neck reconstruction in unique global health crisis. Vigilant use of proper PPE and adherence to the ethical principles proves to be the only shield that will benefit patients, HCW and health system.

Effects of Tungsten Disulphide Coating on Tapered Microfiber for Relative Humidity Sensing Applications.

Tungsten disulphide (WS2) is a two-dimensional transition-metal dichalcogenide material that can be used to improve the sensitivity of a variety of sensing applications. This study investigated the effect of WS2 coating on tapered region microfiber (MF) for relative humidity (RH) sensing applications. The flame brushing technique was used to taper the standard single-mode fiber (SMF) into three different waist diameter sizes of MF 2, 5, and 10 µm, respectively. The MFs were then coated with WS2 via a facile deposition method called the drop-casting technique. Since the MF had a strong evanescent field that allowed fast near-field interaction between the guided light and the environment, depositing WS2 onto the tapered region produced high humidity sensor sensitivity. The experiments were repeated three times to measure the average transmitted power, presenting repeatability and sensing stability. Each MF sample size was tested with varying humidity levels. Furthermore, the coated and non-coated MF performances were compared in the RH range of 45-90% RH at room temperature. It was found that the WS2 coating on 2 µm MF had a high sensitivity of 0.0861 dB/% RH with linearity over 99%. Thus, MF coated with WS2 encourages enhancement in the evanescent field effect in optical fiber humidity sensor applications.

Radiological outcome of acute subtrochanteric fractures fixed with Recon intramedullary nailing, a retrospective case series.

The aim of this study was to evaluate the radiological outcome of acute subtrochanteric fractures fixed with Recon intramedullary nail. Charts of 48 patients with subtrochanteric fractures treated with Recon IM Nailing from January 2014 to December 2015 were retrospectively reviewed. Thirty (62%) patients were male and 18 (38%) were female. The mean age was 52±7 years. The most common mechanism of injury was road traffic accident (RTA) which was in 27 (56%) patients followed by a history of fall in 18 (38%) patients. Mean Radiological Healing time was 14±2 weeks. The mean duration of surgery was 2.27±1 hours while Mean Hospital Stay was 5±2 days. Four patients had delayed fracture healing. This study suggests that intramedullary nailing in Recon Mode is a reliable and effective device especially for subtrochanteric fractures, leading to a high rate of bone union and minimal complications.

Outcome of percutaneous screw fixation of posterior pelvic ring injuries.

OBJECTIVE: To evaluate the clinical outcome of percutaneous fixation for unstable pelvic ring injury. METHODS: This retrospective study was conducted at orthopaedics section of Aga Khan University Hospital Karachi, Pakistan from July 2015 to December 2018. Data was retrieved from trauma registry from July 2015 till December 2018, including all patients who underwent percutaneous fixation for pelvic ring injury. Majeed pelvic score was used to determine the functional outcome. RESULTS: A total number of 30 patients were included, 27(90.0%) adults, and 3(10.0%) paediatrics patients. There were 21(70.0%) males and 9(30.0%)females. . Mean age of patients was 37.1±16.1 years. Post op mean Majeed functional pelvic Score was 85.8. Of the 30 patients, 18 (60.0%) had Excellent, 10 (33.3%) good and 02(6.7%) fair scoring. CONCLUSIONS: Percutaneous fixation of posterior ring injuries has excellent functional outcome, with minimal blood loss and no soft tissue striping..

New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment.

The similarity of spatial structure between radicicol and matrine urged us to perform conformation modification of matrine, followed by L-shaped matrine derivatives, 6, 12, 21a-h and 22a-h were originally designed, synthesized and evaluated for Hsp90N inhibitors as anticancer agents. TSA (Thermal Shift Assay) results indicated that 21e, 22a-c and 22e-g exhibited strong binding force against Hsp90N with∣ΔTm∣ > 3, meanwhile, MTT assay also revealed these compounds displayed potent anticancer activity with IC50 values below 25 µM against HepG2, HeLa and MDA-MB-231 cells lines. Then, compound 22g with a high ΔTm = 10.92 was chosen as a representative to perform further mechanism study. It can induce cell apoptosis, arrest the cell cycle at the S phase and decrease the expression level of Hsp90 in Hela cell. These results originally provided targeted modification strategy for matrine derivatives to serve as Hsp90 inhibitors for cancer therapy.

Anti-cancer potential of sophoridine and its derivatives: Recent progress and future perspectives.

Cancer is the second leading cause of mortality and has resulted in about 9.6 million deaths around the world in 2018. Cancer-caused deaths are expected to be 11.5 million by 2030 all over the world. Because of the fatal nature of cancer, substantial efforts are made all over the world to combat it. Phytoconstituents such as certain alkaloids, saponins, tannins, polyphenols, and terpenoids exhibit anticancer effects. Sophoridine is a tetracyclic quinolizidine alkaloid isolated from the stem and leaves of medicinal plants Sophora alopecuroides L., and Euchresta japonica Benth, and roots of Sophora alopecuroides Ait. Chinese Food and Drug Administration (CFDA) approved sophoridine as an antitumor agent in 2005. This review covers the antitumor activities of sophoridine and its derivatives. The efficacy of sophoridine analogs is expressed with respect to their half-maximal inhibitory concentration (IC50 values). Structure-activity relationship (SAR) study for most of the sophoridine derivatives has been explained. Moreover, the current market of anticancer drugs and its expected growth are discussed. Prospects provide suggestions and clues for novel sophoridine-based anticancer agents with enhanced expected efficacy and minimum toxicity.

Detailed thrombogenicity phenotyping and 1 year outcomes in patients undergoing WATCHMAN implantation: (TARGET-WATCHMAN) a case-control study.

The relation of device related thrombosis (DRT) and major bleeding after left atrial appendage closure (LAAC) to laboratory thrombosis and hemostasis markers has not been studied. We performed a prospective case control study to identify clinical characteristics and laboratory markers in patients who developed DRT and major bleeding following WATCHMAN LAAC. Thromboelastography, platelet aggregation (PA), urinary 11-dehydrothromboxane B2 (UTX), fibrinogen, D-dimer, thrombin time and von Willebrand factor activity were determined at baseline, immediately following, and at 45 and 180 days post-LAAC (n = 32) and outcomes were followed for 1 year. Baseline characteristics and thrombogenic profiles of patients with and without DRT and/or BARC bleeding were compared. Mean age was 76 ± 8 years and CHADS2 VASc score was 4.4 ± 1.4. There were 3 DRTs (2 within 6 months, and 1 at 12 months), 4 Type 3A BARC bleeds, and 2 non-cardiac deaths. Patients with DRT had higher baseline thrombin-induced platelet-fibrin clot strength (68.0 ± 1.8 vs. 62.7 ± 4.7 mm, p = 0.06); FCS (35.6 ± 6.0 vs. 24.4 ± 6.6 mm, p = 0.009); and D-dimer (1712 ± 2330 vs. 283 ± 213 ng/mL, p = 0.001). At baseline, 5 patients had all 3 factors associated with high thrombotic risk and 2 experienced a DRT within 6 months. Patients with Type 3A BARC bleeding had lower baseline collagen-induced and 45-day ADP-induced PA (p < 0.01 for both). DRT following LAAC was associated with a baseline prothrombogenic profile whereas bleeding was associated with low platelet reactivity. These preliminary findings warrant further validation and have future implications on patient selection and adjunctive antithrombotic therapy following LAAC.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622 .

Post-traumatic stress disorder and association with low birth weight in displaced population following conflict in Malakand division, Pakistan: a case control study.

BACKGROUND: The northern part of the province of Khyber Pakhtunkhwa in Pakistan experienced armed conflict since September 2007 till the autumn of 2011. Conflict involved widespread insurgency activity and military intervention including in 2009 internally displacing the 2.5 million people of the valley of Swat to live in camps, with relatives, or in rented accommodation across the region for approximately 4 months. It was during this period the current study was conducted to determine whether Post-Traumatic Stress Disorder in pregnant women was independently associated with Low Birth Weight (LBW) in an area affected by conflict and militancy. METHODS: A case control study was conducted in tertiary care hospitals of district Peshawar, Khyber Pakhtunkhwa. Two hundred twenty-five cases (neonates with birth weight <  2.5 kg) and 225 controls (neonates with birth weight of > 2.5 kg) were enrolled within 24 h of delivery. Post-Traumatic Stress Disorder was assessed through the MINI Neuropsychiatric Interview 5.0, a validated questionnaire along with the birth weight of the newborn. Maternal anthropometry, anemia and other sociodemographic details were also obtained during data collection. Data was analyzed using statistical package (STATA version 14). Logistic regression analysis of the association between LBW and all variables collected with a p-value of < 0.25 on uni-variate analysis were entered. RESULTS: A total of 450 newborn and mother pairs participated in the study with 225 cases and 225 controls. On univariate analysis factors significantly associated with LBW include: less than 5 years of paternal schooling and PTSD. On logistic regression, PTSD was independently associated with low birth weight in the presence of other factors like maternal/paternal schooling, gravida, history of preterm, BMI of the mother and maternal anemia. CONCLUSION: PTSD was found to be independently associated with LBW. In light of the current findings and other similar literature, intervention programs should be considered for pregnant women exposed to traumatic events.