Epilepsy is a chronic neurologic disorder result from electrical disturbances that lead to abnormal discharge of neurons within the CNS. This discharge produced unprovoked and recurrent seizures which alter the normal brain functions. These functional alterations often give rise to behavioral abnormalities, with devastating effect on the patients and their families. To date, major advancement has been done in the treatment of epilepsy, but still, epilepsy is a great challenge in the medicine field which pays attention towards the invention of new and more potential AEDs. Regardless of latest advancement in the epilepsy, an about one third population is unresponsive. So, the proposed underlying mechanism of transfer of normal brain to epileptic is still unanswered and this highlight to identify new targets of drug treatement. For it , we established the seizure threshold, and used exogenous antiepileptogenic mediator i.e., isoxylitones [E/Z] to evaluate if this can control the over expressed JAK-STAT pathway in the model of epileptogenesis and finally discuss the attempts to halt the process of epileptogenesis by regulating the JAK-STAT pathway. From ancient time to present, there is a strong history of usage of plants and their extracts in the treatment of different neurological disorders. Delphinium denudatum is a medicinal plant of Himalayas and Kashmir, locally called Jadwar. This plant is claimed by many local practitioners to be used in seizure treatment. The novel antiepileptic compound ISO[E/Z] was initially isolated from the same plant and later it was synthesized. Previous studies in our lab already reported that ISO[E/Z] have potent antiepileptic effect. It is able to reduce the seizures in kindling model of epileptogenesis. This inhibition of seizure was further confirmed by modulation of BDNF, cfos and through blockage of sodium channel. In current study, we explored the effect of ISO[E/Z] at the molecular and cellular level by targeting JAK-STAT pathway, that is involved in the epileptogenesis process. The ISO[E/Z] was re-synthesized by our collaborator’s team, X therefore in order to validate and standardize the fresh supply of ISO[E/Z], we re-tested the compound both in acute and chronic seizure model. This step was carried out in order to keep compliance with previous findings. For present study, we choose JAK-1, JAK-3, STAT-2 and STAT-5a isoforms of JAK-STAT pathway due to their importance and involvement in the process of epileptogenesis. We found over expression of mRNA and protein of the above mentioned biomarkers in both cortex and hippocampus of untreated PTZ-kindled group. However, the treatment of ISO[E/Z] was able to reduced the JAK-1, JAK-3, STAT-2 and STAT5a expression. These findings suggest that ISO[E/Z] can halt the epileptogenesis progression by interrupting the underlying functional changes at molecular level. Moreover, our findings also validate our previous studies on isoxylitones with a promising compliance. In the light of all these observations, it can be said that isoxylitones in future would be a potential AED in the treatment of refractory epilepsy. At this stage, promising data support the further development of ISO[E/Z] as an inhibitor of JAK-STAT pathway and this strategy is expected to be valuable to modify or prevent the epilepsy. We think, for an adequate control, it is necessary to used a combination of drugs that hit the multiple targets which are the main players underlying epileptogenesis.
قوانین حدود و قصاص میں ہونے والی ترامیم اسلامی جمہوریہ پاکستان میں عوام الناس کا رجحان زیادہ تر مذہب کی طرف ہے اور وہ چاہتے ہیں کہ اس مملکت خداداد میں اسلامی قوانین کا نفاذ اور عمل درآمد ہو لیکن اندرونی و بیرونی مداخلت کی بنا پر حدود وقصاص آرڈیننس میں مند رجہ ذیل ترامیم کی گئی ہیں: قصاص و دیت ایکٹ میں ہونے والی ترامیم قصاص اور دیت ایکٹ سے قبل صدر پاکستان اپنے اختیار کے ذریعے سے کسی بھی مجرم کی قصاص و دیت کے تحت سزا میں کمی یا تخفیف یا ختم کرنے کا اختیار رکھتا تھا ۔ اس قانون کے ذریعے قصاص و دیت سے متعلق جرائم کی سزا میں کسی بھی قسم کی تخفیف کے صدارتی اختیار کو مقتول کے ورثاء کی مرضی سے مشروط کر دیا گیاہے جس کے پیش نظر قصا ص و دیت ایکٹ 1997 کے تحت دفعات 53 تا 55 تعزیرات پاکستان میں ترامیم کی گئیں، جو کہ اوپر تفصیلی طور پر The Criminal Law (Amendment) Act 1997دفعات 2 سے 6 میں بیان ہو چکے ہیں۔ حدود آرڈیننس میں کی جانے والی ترامیم حدود آرڈیننس میں بھی وقت کے گرزنے کے ساتھ ساتھ کچھ تبدیلیاں کی گئی ہیں ،۔ یہ تبدیلیانں زیادہ ترزنا کے حوالے سے ہوئی ہیں ۔ یہ تبدیلیاں مندرجہ ذیل ہیں:
Performance appraisal is a key human resource practice and source of a motivation for an employee and its success depends on justice perception of an employee towards performance appraisal system. Pakistani banking sector is playing a vital role in the economic growth of the country. Private Banks are innovative and effective in their approach as compared to the public banks. Past studies have compared the public and private banks and found that new private banks are more effective than public banks in terms of technical and economic efficiency. However, there are meager studies available in the context of justice perception of performance appraisal practices in the public and private banks. Data were collected through five-point Likert scale and analyzed with SPSS 24.0 versions. In the result difference of justice is measured by mean differences and independent sample t-test. However, it is found that employees of private banks perceive greater justice as compared to public banks. This study emphasizes the importance of fairness perception of employees in the context of performance appraisal practices and could be used to better understand the problems associated with appraisal practices in public and private banks.
Purpose: to compare umbilical artery and middle cerebral Doppler ultrasound values in normal and high risk pregnancies with fetal outcome.
Method: 121 consecutive pregnancies (at or over 28 weeks gestation), stratified into low and high risk pregnancies based on clinician information were prospectively examined with doppler ultrasound of UA and MCA.
Results: outcome was available for 100 of the 121 patients. 26% of pregnancies had poor outcome. Of these 73% (19) and 27% (7) were classified as high risk and low risk respectively. UA alone or in combination with MCA was shown to have 100% specificity for predicting fetal outcome. However, sensitivities and negative predictive values were poor, ranging from 8-21% and 17-35% respectively. Better positive predictive values were registered in MCA in comparison to those of UA (PPV of 44% and 83% in high risk and low risk categories respectively versus PPV of 0% in both UA high and low risk categories respectively). However, MCA specificities were lower at 80% and 85% for high and low risk pregnancies respectively.
Conclusion: the combination of UA and MCA doppler ultrasound examinations is very specific in predicting fetal outcome. However, the sensitivities, positive and negative predictive values were low.