Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Role of zinc in chronic telogen effluvium in serum and hair of patients with alopecia.

Objectives: To determine the levels of zinc in hair and serum samples of chronic telogen effluvium patients. METHODS: The case-control study was conducted at the Dow University of Health Sciences, Karachi, from April 2017 to May 2018, and comprised diagnosed cases of chronic telogen effluvium in group A, and healthy controls matched for age and gender in group B. Hair pull test was done, and level of zinc in hair and serum samples was determined using atomic absorption spectrophotometer. Data was analysed using SPSS 21. RESULTS: Of the 100 subjects, 50(50%) were in group A; 28(56%) females ad 22(44%) males with mean age 27.46±4.98 years. There were 50(50%) subejcts in group B; 26(52%) males ad 24(48%) females with mean age 28.34±4.92 years (p>0.05). Significantly low levels of zinc were observed in serum as well as hair samples in group A compared to group B (p<0.05). A positive significant association was observed in the level of zinc in hair with their concentration in the serum of subjects in both the groups (r=0.310, p<0.05). CONCLUSIONS: Low levels of zinc in hair and serum were found to be associated with chronic telogen effluvium.

Continuous and intermittent theta burst stimulation of primary visual cortex do not modulate resting state functional connectivity: A sham-controlled multi-echo fMRI study.

INTRODUCTION: Theta burst stimulation (TBS) is a type of rTMS protocol which has the advantage of a shorter delivery time over traditional rTMS. When applied to motor cortex, intermittent TBS (iTBS) has been shown to yield excitatory aftereffects, whereas continuous TBS (cTBS) may lead to inhibitory aftereffects, both lasting from minutes to hours. The majority of TBS research has targeted motor, frontal, and parietal regions, and to date very few studies have examined its efficacy at visual areas. We designed a sham-controlled study to investigate the immediate poststimulation and short-term (1 h post-stimulation) effects of iTBS and cTBS to V1. METHODS: Using multiecho functional magnetic resonance imaging, we measured the direct and indirect effects of TBS by comparing resting state functional connectivity (FC) before and after stimulation in whole brain networks, and seeds from V1 (stimulation site) and neighboring occipital and parietal visual networks. In addition, we also measured pre- and post-TBS phosphene thresholds (PTs) to examine the modulatory effects of TBS on cortical excitability. RESULTS: We found no changes in FC for iTBS, cTBS or sham stimulation conditions from baseline to poststimulation timepoints. Additionally, cTBS and iTBS had no effect on visual cortical excitability. CONCLUSIONS: Our results indicate that unlike our previous low frequency rTMS to V1 study, which resulted in widespread FC changes up to at least 1 h after stimulation, TBS to V1 does not affect FC. Contrary to the studies showing comparable TBS and rTMS aftereffects in motor and frontal regions, our findings suggest that a single session of cTBS or iTBS to V1 at 80% PT using a standard protocol of 600 pulses may not be effective in targeting FC, especially in clinical settings where therapy for pathological networks is the goal.

Modulating intrinsic functional connectivity with visual cortex using low-frequency repetitive transcranial magnetic stimulation.

INTRODUCTION: Intrinsic network connectivity becomes altered in pathophysiology. Noninvasive brain stimulation can modulate pathological functional networks in an attempt to restore the inherent response. To determine its usefulness for visual-related disorders, we developed procedures investigating repetitive transcranial magnetic stimulation (rTMS) protocols targeting the visual cortex on modulating connectivity associated with the visual network and default mode network (DMN). METHODS: We compared two low-frequency (1 Hz) rTMS protocols to the visual cortex (V1)-a single 20 min session and five successive 20 min sessions (accelerated/within-session rTMS)-using multi-echo resting-state functional magnetic resonance whole-brain imaging and resting-state functional connectivity (rsFC). We also explored the relationship between rsFC and rTMS-induced changes in key inhibitory and excitatory neurotransmitters, γ-aminobutyric acid (GABA) and glutamate. GABA (GABA+) and glutamate (Glx) concentrations were measured in vivo using magnetic resonance spectroscopy. RESULTS: Acute disruption with a single rTMS session caused widespread connectivity reconfiguration with nodes of interest. Changes were not evident immediately post-rTMS but were observed at 1 h post-rTMS. Accelerated sessions resulted in weak alterations in connectivity, producing a relatively homeostatic response. Changes in GABA+ and Glx concentrations with network connectivity were dependent on the rTMS protocol. CONCLUSIONS: This proof-of-concept study offers new perspectives to assess stimulation-induced neural processes involved in intrinsic functional connectivity and the potential for rTMS to modulate nodes interconnected with the visual cortex. The differential effects of single-session and accelerated rTMS on physiological markers are crucial for furthering the advancement of treatment modalities in visual cortex related disorders.

Continuous and intermittent theta burst stimulation to the visual cortex do not alter GABA and glutamate concentrations measured by magnetic resonance spectroscopy.

BACKGROUND: Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), uses repeated high-frequency bursts to non-invasively modulate neural processes in the brain. An intermittent TBS (iTBS) protocol is generally considered "excitatory," while continuous TBS (cTBS) is considered "inhibitory." However, the majority of work that has led to these effects being associated with the respective protocols has been done in the motor cortex, and it is well established that TMS can have variable effects across the brain. OBJECTIVES AND METHOD: We investigated the effects of iTBS and cTBS to the primary visual cortex (V1) on composite levels of gamma-aminobutyric acid + co-edited macromolecules (GABA+) and glutamate + glutamine (Glx) since these are key inhibitory and excitatory neurotransmitters, respectively. Participants received a single session of cTBS, iTBS, or sham TBS to V1. GABA+ and Glx were quantified in vivo at the stimulation site using spectral-edited proton magnetic resonance spectroscopy (1 H-MRS) at 3T. Baseline pre-TBS GABA+ and Glx levels were compared to immediate post-TBS and 1 h post-TBS levels. RESULTS: There were no significant changes in GABA+ or Glx following either of the TBS conditions. Visual cortical excitability, measured using phosphene thresholds, remained unchanged following both cTBS and iTBS conditions. There was no relationship between excitability thresholds and GABA+ or Glx levels. However, TBS did alter the relationship between GABA+ and Glx for up to 1 h following stimulation. CONCLUSIONS: These findings demonstrate that a single session of TBS to the visual cortex can be used without significant effects on the tonic levels of these key neurotransmitters; and add to our understanding that TBS has differential effects at visual, motor, and frontal cortices.

Impact of Oral Health Educational Interventions on Oral Hygiene Status of Children with Hearing Loss: A Randomized Controlled Trial.

INTRODUCTION: Oral health is considered as one of the essential components of the overall health of every individual. Maintaining oral health is a gradual process that requires commitment. Children who require special care such as hearing impairment experience difficulty in maintaining oral health primarily due to communication difficulties. This study is aimed at using different interventions to evaluate the improvement of oral hygiene in hearing impaired children. MATERIALS AND METHODS: Fifty-nine children were recruited in this study that were allocated randomly into each group with twenty children as follows: group 1: pictorial, group 2: video, and group 3: control. Mean plaque and gingival scores were noted before and after the use of different interventions. Oral hygiene was categorized as "excellent," "good," and "fair." Gingival health was categorized as "healthy," "mild gingivitis," and "moderate gingivitis." RESULTS: Thirty-four children (57.6%) were from 12-13 years of age bracket, and 25 (42.4%) belonged to 14-16 years of age. Regarding gender, there were 37 (62.7%) males and 22 (37.3%) females. About comparison of mean gingival and plaque scores before and after interventions in each group, a significant difference was found in group 1 (p < 0.001) and group 2 (p < 0.001), as compared to group 3 where the difference in scores was not significant (p > 0.05). CONCLUSION: Maintaining oral health requires the compliance of individuals to perform different methods of preventive dentistry, such as tooth brushing and use of dental floss. The use of different oral hygiene educational interventions such as pictorial and video methods have been proven and useful for hearing impaired children in improving oral health.

Reliance on visual feedback from ocular accommodation on motor skills in children with developmental coordination disorder and typically developing controls.

Children with developmental coordination disorder (DCD) present with marked impairments in motor skills, including visual-motor integration. Oculomotor anomalies are more prevalent in children with DCD than typically developing children. Children with DCD further demonstrate altered use of visual feedback compared to typically developing controls. We investigated whether the accommodation system, a key component of the oculomotor system, contributes to visual feedback during fine and gross motor skills performance; and whether children with DCD demonstrate differences in reliance on visual feedback from accommodation. Minus dioptre lenses were used to maximally induce accommodation and impede accommodation dynamics. Children with DCD and typically developing controls performed motor skills tests assessing balance, upper limb coordination, visual-motor performance, gross and fine dexterity. Motor skills performance in controls was significantly affected by impeded accommodation in all tasks. Children with DCD demonstrated reliance on accommodation feedback in upper limb and visual-motor tasks only. Children with DCD may be less reliant on visual feedback obtained from accommodation due to adaptive mechanisms to overcome faulty information in the presence of oculomotor anomalies. These results strengthen our previous findings that accommodation anomalies contribute to motor skills impairment, and suggest that performance on these motor tasks is heavily reliant on visual feedback from accommodation.

Case-control study for assessment of factors associated with periodontitis among adults attending a university hospital in Karachi, Pakistan.

OBJECTIVE: To compare the physiological and biochemical markers in healthy and periodontitis subjects, and to relate these markers with the periodontal health condition. METHOD: The case-control study was conducted at the Dow University of Health Sciences, Karachi, from April 2017 to March 2018, and comprised systematically healthy controls and periodontitis cases. Periodontal probing depth, clinical attachment loss, oral hygiene indices, educational status and body mass index were recorded for all the subjects. Serum levels of biochemical markers, including calcium, phosphate and interleukin-6, were also measured. Data was analysed using SPSS 16. RESULTS: Of the 150 subjects, 75(50%) each were in the case and control groups. The overall mean age was 31.23±3.7 years (range: 22-42 years). The cases had relatively poor oral hygiene indices and educational status compared to the controls (p<0.05). Serum calcium level was lower, whereas mean body mass index was higher in the cases compared to the controls (p<0.05). No significant difference was found in interleukin-6 and phosphate levels (p>0.05). Clinical attachment loss showed significant correlation (p<0.05). CONCLUSIONS: Low serum calcium and educational levels, higher body mass index and poor oral hygiene were found to be the risk factors for the progression of periodontitis.

Assessing differential effects of single and accelerated low-frequency rTMS to the visual cortex on GABA and glutamate concentrations.

BACKGROUND: The application of repetitive transcranial magnetic stimulation (rTMS) for therapeutic use in visual-related disorders and its underlying mechanisms in the visual cortex is under-investigated. Additionally, there is little examination of rTMS adverse effects particularly with regards to visual and cognitive function. Neural plasticity is key in rehabilitation and recovery of function; thus, effective therapeutic strategies must be capable of modulating plasticity. Glutamate and γ-aminobutyric acid (GABA)-mediated changes in the balance between excitation and inhibition are prominent features in visual cortical plasticity. OBJECTIVES AND METHOD: We investigated the effects of low-frequency (1 Hz) rTMS to the visual cortex on levels of neurotransmitters GABA and glutamate to determine the therapeutic potential of 1 Hz rTMS for visual-related disorders. Two rTMS regimes commonly used in clinical applications were investigated: participants received rTMS to the visual cortex either in a single 20-min session or five accelerated 20-min sessions (not previously investigated at the visual cortex). Proton (1H) magnetic resonance spectroscopy for in vivo quantification of GABA (assessed via GABA+) and glutamate (assessed via Glx) concentrations was performed pre- and post-rTMS. RESULTS: GABA+ and Glx concentrations were unaltered following a single session of rTMS to the visual cortex. One day of accelerated rTMS significantly reduced GABA+ concentration for up to 24 hr, with levels returning to baseline by 1-week post-rTMS. Basic visual and cognitive function remained largely unchanged. CONCLUSION: Accelerated 1 Hz rTMS to the visual cortex has greater potential for approaches targeting plasticity or in cases with altered GABAergic responses in visual disorders. Notably, these results provide preliminary insight into a critical window of plasticity with accelerated rTMS (e.g., 24 hr) in which adjunct therapies may offer better functional outcome. We describe detailed procedures to enable further exploration of these protocols.

Altered white matter structure in auditory tracts following early monocular enucleation.

PURPOSE: Similar to early blindness, monocular enucleation (the removal of one eye) early in life results in crossmodal behavioral and morphological adaptations. Previously it has been shown that partial visual deprivation from early monocular enucleation results in structural white matter changes throughout the visual system (Wong et al., 2018). The current study investigated structural white matter of the auditory system in adults who have undergone early monocular enucleation compared to binocular control participants. METHODS: We reconstructed four auditory and audiovisual tracts of interest using probabilistic tractography and compared microstructural properties of these tracts to binocularly intact controls using standard diffusion indices. RESULTS: Although both groups demonstrated asymmetries in indices in intrahemispheric tracts, monocular enucleation participants showed asymmetries opposite to control participants in the auditory and A1-V1 tracts. Monocular enucleation participants also demonstrated significantly lower fractional anisotropy in the audiovisual projections contralateral to the enucleated eye relative to control participants. CONCLUSIONS: Partial vision loss from early monocular enucleation results in altered structural connectivity that extends into the auditory system, beyond tracts primarily dedicated to vision.

The relationship of 1,25-dihydroxyvitamin D and Vitamin D binding protein in periodontitis.

OBJECTIVE: This study was conducted to explore the relationship between 1,25-dihydroxy vitamin D (1,25(OH)2D) and Vitamin-D binding protein (DBP) in patients with periodontitis and healthy controls. METHODS: Seventy-five periodontitis cases were recruited from the dental OPD of Dow University of Health Sciences, Karachi. Diagnostic criteria of periodontitis were followed according to the probe pocket depth and clinical attachment loss. Seventy-five periodontal healthy controls were selected from the faculty and students of same university. Serum levels of 1,25(OH)2D and DBP were determined by ELISA. RESULTS: Significantly low levels of 1,25(OH)2D and high levels of serum DBP were observed in periodontitis patients compared to healthy controls (p<0.05), with levels of DBP increasing significantly with the severity of periodontitis (p=0.005). Concentrations of DBP correlated positively with 1,25(OH)2D, especially in cases with periodontitis (r =0.780; p<0.001). CONCLUSION: Within the limits of the study, we conclude that low 1,25(OH)2D levels and high DBP levels are associated with periodontitis.

Altered white matter connectivity associated with visual hallucinations following occipital stroke.

INTRODUCTION: Visual hallucinations that arise following vision loss stem from aberrant functional activity in visual cortices and an imbalance of activity across associated cortical and subcortical networks subsequent to visual pathway damage. We sought to determine if structural changes in white matter connectivity play a role in cases of chronic visual hallucinations associated with visual cortical damage. METHODS: We performed diffusion tensor imaging (DTI) and probabilistic fiber tractography to assess white matter connectivity in a patient suffering from continuous and disruptive phosphene (simple) visual hallucinations for more than 2 years following right occipital stroke. We compared these data to that of healthy age-matched controls. RESULTS: Probabilistic tractography to reconstruct white matter tracts suggests regeneration of terminal fibers of the ipsilesional optic radiations in the patient. However, arrangement of the converse reconstruction of these tracts, which were seeded from the ipsilesional visual cortex to the intrahemispheric lateral geniculate body, remained disrupted. We further observed compromised structural characteristics, and changes in diffusion (measured using diffusion tensor indices) of white matter tracts in the patient connecting the visual cortex with frontal and temporal regions, and also in interhemispheric connectivity between visual cortices. CONCLUSIONS: Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493-1500). Long-term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations.

Altered white matter structure in the visual system following early monocular enucleation.

Partial visual deprivation from early monocular enucleation (the surgical removal of one eye within the first few years of life) results in a number of long-term morphological adaptations in adult cortical and subcortical visual, auditory, and multisensory brain regions. In this study, we investigated whether early monocular enucleation also results in the altered development of white matter structure. Diffusion tensor imaging and probabilistic tractography were performed to assess potential differences in visual system white matter in adult participants who had undergone early monocular enucleation compared to binocularly intact controls. To examine the microstructural properties of these tracts, mean diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted bilaterally. Asymmetries opposite to those observed in controls were found for FA, MD, and RD in the optic radiations, the projections from primary visual cortex (V1) to the lateral geniculate nucleus (LGN), and the interhemispheric V1 projections of early monocular enucleation participants. Early monocular enucleation was also associated with significantly lower FA bidirectionally in the interhemispheric V1 projections. These differences were consistently greater for the tracts contralateral to the enucleated eye, and are consistent with the asymmetric LGN volumes and optic tract diameters previously demonstrated in this group of participants. Overall, these results indicate that early monocular enucleation has long-term effects on white matter structure in the visual pathway that results in reduced fiber organization in tracts contralateral to the enucleated eye. Hum Brain Mapp 39:133-144, 2018. © 2017 Wiley Periodicals, Inc.

Consecutive TMS-fMRI reveals remote effects of neural noise to the "occipital face area".

The human cortical system for face perception comprises a network of connected regions including the middle fusiform gyrus ("fusiform face area" or FFA), the inferior occipital gyrus ("occipital face area" or OFA), and the posterior superior temporal sulcus (pSTS). Here, we sought to investigate how transcranial magnetic stimulation (TMS) to the OFA affects activity within the face processing network. We used offline repetitive TMS to temporarily introduce neural noise in the right OFA in healthy subjects. We then immediately performed functional magnetic resonance imaging (fMRI) to measure changes in blood oxygenation level dependent (BOLD) signal across the face network using an fMR-adaptation (fMR-A) paradigm. We hypothesized that TMS to the right OFA would induce abnormal face identity coding throughout the face processing network in regions to which it has direct or indirect connections. Indeed, BOLD signal for face identity, but not non-face (butterfly) identity, decreased in the right OFA and FFA following TMS to the right OFA compared to both sham TMS and TMS to a control site, the nearby object-related lateral occipital area (LO). Further, TMS to the right OFA decreased face-related activation in the left FFA, without any effect in the left OFA. Our findings indicate that TMS to the right OFA selectively disrupts face coding at both the stimulation site and bilateral FFA. TMS to the right OFA also decreased BOLD signal for different identity stimuli in the right pSTS. Together with mounting evidence from patient studies, we demonstrate connectivity of the OFA within the face network and that its activity modulates face processing in bilateral FFA as well as the right pSTS. Moreover, this study shows that deep regions within the face network can be remotely probed by stimulating structures closer to the cortical surface.

rTMS reduces cortical imbalance associated with visual hallucinations after occipital stroke.

OBJECTIVE: To investigate the efficacy of multiday repetitive transcranial magnetic stimulation (rTMS) to the occipital cortex in a patient with continuous visual phosphene hallucinations for more than 2 years following occipital stroke. METHODS: Low-frequency rTMS (1 Hz) was applied to the lesion site for 30 minutes daily over 5 consecutive days. Functional MRI (fMRI) was performed before and after rTMS treatment. RESULTS: Increased application of rTMS corresponded with a reduction in intensity of visual phosphene hallucinations and was reflected in altered blood oxygen level-dependent signal. fMRI revealed focal excitatory discharges at the border of the lesion, highlighting the origin of phosphenes. Post-rTMS, rTMS did not simply suppress activity in the patient but rather redistributed the previously imbalanced cortical activity not only at the stimulation site but in remote cortical regions so that it more closely resembled that of controls. CONCLUSIONS: This case is rare in its presentation of chronic continuous visual phosphene hallucinations following occipital stroke. We present a case of multiday application of rTMS to visual cortex and demonstrate that rTMS provides a valuable therapeutic intervention in modulating visual hallucinations following occipital damage. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence in a single-case report that multiday rTMS reduces intrahemispheric and interhemispheric imbalance and associated visual phosphene hallucinations following occipital stroke.

TMS to object cortex affects both object and scene remote networks while TMS to scene cortex only affects scene networks.

Viewing the world involves many computations across a great number of regions of the brain, all the while appearing seamless and effortless. We sought to determine the connectivity of object and scene processing regions of cortex through the influence of transient focal neural noise in discrete nodes within these networks. We consecutively paired repetitive transcranial magnetic stimulation (rTMS) with functional magnetic resonance-adaptation (fMR-A) to measure the effect of rTMS on functional response properties at the stimulation site and in remote regions. In separate sessions, rTMS was applied to the object preferential lateral occipital region (LO) and scene preferential transverse occipital sulcus (TOS). Pre- and post-stimulation responses were compared using fMR-A. In addition to modulating BOLD signal at the stimulation site, TMS affected remote regions revealing inter and intrahemispheric connections between LO, TOS, and the posterior parahippocampal place area (PPA). Moreover, we show remote effects from object preferential LO to outside the ventral perception network, in parietal and frontal areas, indicating an interaction of dorsal and ventral streams and possibly a shared common framework of perception and action.

Relationship of ocular accommodation and motor skills performance in developmental coordination disorder.

Ocular accommodation provides a well-focussed image, feedback for accurate eye movement control, and cues for depth perception. To accurately perform visually guided motor tasks, integration of ocular motor systems is essential. Children with motor coordination impairment are established to be at higher risk of accommodation anomalies. The aim of the present study was to examine the relationship between ocular accommodation and motor tasks, which are often overlooked, in order to better understand the problems experienced by children with motor coordination impairment. Visual function, gross and fine motor skills were assessed in children with developmental coordination disorder (DCD) and typically developing control children. Children with DCD had significantly poorer accommodation facility and amplitude dynamics compared to controls. Results indicate a relationship between impaired accommodation and motor skills. Specifically, accommodation anomalies correlated with visual motor, upper limb and fine dexterity task performance. Consequently, we argue accommodation anomalies influence the ineffective coordination of action and perception in DCD. Furthermore, reading disabilities were related to poorer motor performance. We postulate the role of the fastigial nucleus as a common pathway for accommodation and motor deficits. Implications of the findings and recommended visual screening protocols are discussed.