Tuberculosis prevalence and demographic characteristics of population in Azad Jammu and Kashmir (Pakistan): A retrospective study.

Tuberculosis (TB) remains a serious problem for public health and a leading cause of death after COVID-19 and superior to even HIV/AIDS. It is a social health issue and can cause stigma and economic loss as the person cannot perform professionally due to lethargy caused by disease. It is a retrospective study done on data from National TB program Muzaffarabad chapter. The details were noted on SPSS and analysis was done to find important demographic characteristics. The total number of patients was 3441; among which 48.76% were males. Most of them (81.11%) belonged to the Muzaffarabad division of Azad Jammu and Kahmir (AJK). The microbiologically or culture positive cases were 440. Rifampicin resistance was present in 147 cases, further categorized as high (n = 143), very high (n = 3), or true positive (n = 1) resistance. Muti drug resistance was found in 19 cases. The microscopy culture is more sensitive (AUC = 0.511) than MTB/RIF or serology (AUC = 0.502) according to ROC. The rate of positive smear results is not very satisfactory in the present study as it cannot detect dormant or latent cases. There is a need to establish more sensitive tests for detection of cases and more research to combat the disease.

The Pathological Mechanisms and Treatments of Tinnitus.

Tinnitus is defined as the ringing, hissing, clicking or roaring sounds an individual consciously perceives in the absence of an external auditory stimulus. Currently, the literature on the mechanism of tinnitus pathology is multifaceted, ranging from tinnitus generation at the cellular level to its perception at the system level. Cellular level mechanisms include increased neuronal synchrony, neurotransmission changes and maladaptive plasticity. At the system level, the role of auditory structures, non-auditory structures, changes in the functional connectivities in higher regions and tinnitus networks have been investigated. The exploration of all these mechanisms creates a holistic view on understanding the changes the pathophysiology of tinnitus undertakes. Although tinnitus percept may start at the level of cochlear nerve deafferentation, the neuronal changes in the central auditory system to the neuronal and connectivity changes in non-auditory regions, such as the limbic system, become cardinal in chronic tinnitus generation. At the present moment, some tinnitus generation mechanisms are well established (e.g., increased neuronal synchrony) whereas other mechanisms have gained more traction recently (e.g., tinnitus networks, tinnitus-distress networks) and therefore, require additional investigation to solidify their role in tinnitus pathology. The treatments and therapeutics designed for tinnitus are numerous, with varied levels of success. They are generally two-fold: some treatments focus on tinnitus cessation (including cochlear implants, deep brain stimulation, transcranial direct current stimulation and transcranial magnetic stimulation) whereas the other set focuses on tinnitus reduction or masking (including hearing aids, sound therapy, cognitive behavioral therapy, tinnitus retraining therapy, and tailor made notched musical training).  Tinnitus management has focused on implementing tinnitus masking/reducing therapies more than tinnitus cessation, since cessation treatments are still lacking in streamlined treatment protocols and long-term sustainability and efficacy of the treatment. This review will focus on concisely exploring the current and most relevant tinnitus pathophysiology mechanisms, treatments and therapeutics.

Migrainous Infarction and Cortical Spreading Depression.

Migraine is a very common disorder of the nervous system. It shares similar physiological processes with stroke. Migrainous infarction is a rare complication of migraine with aura. The neuro-logical symptoms of migraine aura correspond to the cortical spreading depression and this depression can lead to a migrainous infarction. It is pertinent to state that the investigation and detection of the cortical depression might have a great clinical significance. Blood vessels in the cranium play an important role in the pathophysiology of migraine.  In the case of injured states of brain, the cortical spreading depression causes extreme vasoconstriction rather than vasodilation. The endothelial damage caused by the cortical spreading depression can result in hypercoagulability, leading to an increased risk of stroke. There are many genetic disorders in which migraine and stroke are the major symptoms and an insight into these disorders can help us in the understanding of complex mechanisms of migrainous infarction. It is pertinent to state that some derangements in the vascular function accompany migraine which may also serve as targets for research and treatment. This article will describe the hemodynamic and genetic relationship between migraine induced stroke and how it relates to the cortical spreading depression.

Epileptic seizures.

Epilepsy is a condition marked by abnormal neuronal discharges or hyperexcitability of neurons with synchronicity and is recognized as a major public health concern. The pathology is categorized into three subgroups: acquired, idiopathic, and epilepsy of genetic or developmental origin. There are approximately 1000 associated genes and the role of γ-aminobutyric acid (GABA) mediated inhibition, as well as glutamate mediated excitation, forms the basis of pathology. Epilepsy is further classified as being of focal, general or unknown onset. Genetic predisposition, comorbidities and novel biomarkers are useful for prediction. Prevalent postictal symptoms are postictal headache and migraine, postictal psychosis and delirium, postictal Todd's paresis and postictal automatisms. Diagnostic methods include electroencephalography (EEG), computed tomography scan, magnetic resonance imaging (MRI), positron emission tomography, single photon emission computed tomography and genetic testing; EEG and MRI are the two main techniques. Clinical history and witness testimonies combined with a knowledge of seizure semiology helps in distinguishing between seizures. Clinical information and patient history do not always lead to a clear diagnosis, in which case EEG and 24-hour EEG monitoring with video recording (video-EEG/vEEG) help in seizure differentiation. Treatment includes first aid, therapeutics such as anti-epileptic drugs, surgery, ketogenic diet and gene therapy. In this review, we are focusing on summarizing published literature on epilepsy and epileptic seizures, and concisely apprise the reader of the latest cutting-edge advances and knowledge on epileptic seizures.