Clinical experience with paliperidone palmitate in a specialty hospital in the Philippines: A short report

Objectives@#This study aimed to describe the clinical outcomes related to theintroduction of Paliperidone Palmitate in a specialty hospital in the Philippines.@*Methodology@#Cross-sectional study among patients with Schizophrenia seen at thepsychiatry service of a specialty hospital catering to war veterans who were initiated onPaliperidone Palmitate. We reviewed and abstracted baseline patient data from themedical record of eligible patients. Outcome of treatment was collected through a one-time objective assessment of the patient by a third-party psychiatrist using theStructured Clinical Interview for Symptoms of Remission (SCI-SR) tool.@*Results@#A total of 30 patients were recruited for the study from August 2020 and June2021, the majority of whom were males (80%), residents of the National Capital Region(50%) and single (20%). The median duration from schizophrenia diagnosis to initiation of Paliperidone treatment was 19.50 years (IQR: 16.60 – 33.50). In eight patients (22.67%),other antipsychotic drugs were discontinued following initiation of Paliperidonetreatment; in the remaining 22 participants (73.33%), Paliperidone was taken concurrentlywith other antipsychotic drugs. The median duration from the initiation of Paliperidonetreatment to follow-up assessment was 27.20 months (IQR: 24.73 – 30.50), with allparticipants having at least 6 months of treatment. At follow-up assessment, allparticipants were classified to be in remission.@*Conclusion@#In this study among patients with schizophrenia seen in a specialtyhospital in the Philippines, we found evidence that clinical outcomes with PaliperidonePalmitate were comparable to those given a combination of oral and long- actingantipsychotics.

A case of neovascular glaucoma secondary to ocular ischemia

Objective@#To present a case of neovascular glaucoma secondary to ocular ischemic syndrome following an uncomplicated phacoemulsification@*Methods@#This is a case description of a 74-year-old male who developed blurred vision and increased intraocular pressure (IOP) two months after an uncomplicated phacoemulsification cataract surgery with posterior chamber lens implantation of the left eye. There was iris neovascularization with absence of retinal dot/blot hemorrhages or neovascularization. The fluorescein angiogram (FA) showed delayed choroidal fluorescence and arteriovenous time. IOP-lowering medications and intravitreal injection of aflibercept were given. Carotid doppler test showed 70% stenosis of the ipsilateral artery but a subsequent magnetic resonance angiography (MRA) did not show evidence of significant stenosis. @*Results@#At his last consultation, visual acuity improved to counting fingers. IOP was maintained at 12 mmHg with one anti-glaucoma medication.@*Conclusion@#Ocular ischemia can confound the outcome of an uncomplicated cataract surgery. Doppler scans are usually chosen as the first-line exam for those suspected of carotid stenosis but, at times, may have contradictory results with MRA.

Rethinking mental health services during the COVID-19 pandemic; Proceedings of the Fourth Southeast Asia Mental Health Forum, 08-09 October 2020, Philippines

@#The COVID-19 pandemic has had pervasive effects on society at large, specifically disrupting routine and established processes at the household, organizational, and community levels. The Philippine Psychiatric Association organized the Fourth Southeast Asia Mental Health Forum to discuss issues and share experiences on how this community can respond to the challenges brought about by the COVID-19 pandemic. Three common challenges for the mental health community were identified – (a) ensuring the continuity of services for persons with psychiatric disorders in different settings; (b) preventing spread of COVID-19 infection in in-patient or residential mental health facilities; and (c) addressing the emergent demand for mental health services from health workers and the general population experiencing psychological symptoms because of the pandemic situation. In the face of these challenges, two broad groups of good practices and innovations were conceptualized and implemented by professionals and institutions: (a) development of alternative arrangements for the delivery of mental health services; and (b) mobilization of stakeholders and resources to ensure whole-of-government and whole-of-society approaches. The lessons and ideas that emerged from the forum may find applicability not only in the next few months during which COVID-19 may persist in our midst (i.e., the “new normal”), but also in other future events that may cause the same level of societal impact and disruption.

Implications of the ammonia distribution on Jupiter from 1 to 100 bars as measured by the Juno microwave radiometer.

The latitude-altitude map of ammonia mixing ratio shows an ammonia-rich zone at 0-5°N, with mixing ratios of 320-340 ppm, extending from 40-60 bars up to the ammonia cloud base at 0.7 bars. Ammonia-poor air occupies a belt from 5-20°N. We argue that downdrafts as well as updrafts are needed in the 0-5°N zone to balance the upward ammonia flux. Outside the 0-20°N region, the belt-zone signature is weaker. At latitudes out to ±40°, there is an ammonia-rich layer from cloud base down to 2 bars which we argue is caused by falling precipitation. Below, there is an ammonia-poor layer with a minimum at 6 bars. Unanswered questions include how the ammonia-poor layer is maintained, why the belt-zone structure is barely evident in the ammonia distribution outside 0-20°N, and how the internal heat is transported through the ammonia-poor layer to the ammonia cloud base.

Inflammatory pigment epithelial detachment associated with Blastocystis hominis

Objective@#To describe a case of inflammatory pigment epithelial detachment (PED) presumed to be secondary to the amoeba Blastocystis hominis.@*Methods@#This is an interventional case report.@*Results@#A 46-year-old male complained of visual distortion in the left eye for 7 months. Examination revealed the presence of a subretinal cystic lesion on the fovea. Optical coherence tomography demonstrated a PED with a hyperreflective lesion over the detached retinal pigment epithelium (RPE). Work-up included a fecalysis, which revealed the presence of Blastocystis hominis. The patient was treated with oral metronidazole. RPE detachment resolved after treatment with no recurrence in 30 months of follow-up.@*Conclusion@#Intestinal parasitic infection may be associated with retinal disease and should be included in the differential diagnosis of PED when OCT reveals a hyperreflective lesion.

Pegaptanib sodium for macular edema due to retinal-vein occlusion among patients intolerant to intravitreal triamcinolone acetonide

Objective@#To report the efficacy and safety of intravitreal pegaptanib sodium (IVP) on macular edema (ME) due to branch retinal-vein occlusion (BRVO) among patients intolerant to intravitreal triamcinolone acetonide (IVTA). @*Methods@#Four eyes with ME due to BRVO were included in this interventional case series. The main outcome measures were best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and adverse effects.@*Results@#There was a significant decrease in mean CMT from 524.50 ± 141.12 to 293.75 ± 130.75 microns (p = 0.009) after IVP injection. BCVA improved in all 4 eyes after IVP. Mean IOP after IVP was 13.60 ± 3.21. No ocular or systemic complications were observed.@*Conclusion@#IVP appears to be safe and effective in decreasing retinal thickness and improving VA in eyes with ME due to BRVO. IVP is a potential treatment for eyes that are intolerant to IVTA.

GABA immunoreactivity in the developing rat thalamus and Otx2 homeoprotein expression in migrating neurons.

We investigated the expression of gamma-aminobutyric acid (GABA) in the developing rat thalamus by immunohistochemistry, using light, confocal and electron microscopy. We also examined the relationship between the expression of the homeoprotein Otx2, a transcription factor implicated in brain regionalization, and the radial and non-radial migration of early generated thalamic neurons, identified by the neuronal markers calretinin (CR) and GABA. The earliest thalamic neurons generated between embryonic days (E) 13 and 15 include those of the reticular nucleus, entirely composed by GABAergic neurons. GABA immunoreactivity appeared at E14 in immature neurons and processes laterally to the neuroepithelium of the diencephalic vesicle. The embryonic and perinatal periods were characterized by the presence of abundant GABA-immunoreactive fibers, mostly tangentially oriented, and of growth cones. At E15 and E16, GABA was expressed in radially and non-radially oriented neurons in the region of the reticular thalamic migration, between the dorsal and ventral thalamic primordia, and within the dorsal thalamus. At these embryonic stages, some CR- and GABA-immunoreactive migrating-like neurons, located in the migratory stream and in the dorsal thalamus, expressed the homeoprotein Otx2. In the perinatal period, the preponderance of GABAergic neurons was restricted to the reticular nucleus and several GABAergic fibers were still detectable throughout the thalamus. The immunolabeling of fibers progressively decreased and was no longer visible by postnatal day 10, when the adult configuration of GABA immunostaining was achieved. These results reveal the spatio-temporal features of GABA expression in the developing thalamus and suggest a novel role of Otx2 in thalamic cell migration.

Laspartomycin, an acidic lipopeptide antibiotic with a unique peptide core.

Laspartomycin was originally isolated and characterized in 1968 as a lipopeptide antibiotic related to amphomycin. The molecular weight and structure remained unknown until now. In the present study, laspartomycin was purified by a novel calcium chelate procedure, and the structure of the major component (1) was determined. The structure of laspartomycin C (1) differs from that of amphomycin and all related antibiotics as a result of its peptide region being acidic rather than amphoteric and the amino acid branching into the side chain being diaminopropionic rather than diaminobutyric. In addition, the fatty acid side chain is 2,3-unsaturated compared to 3,4-unsaturated for amphomycin and other related antibiotics. Calcium ion addition to stabilize a particular conformer was found to be important for an enzymatic deacylation of the antibiotic. A peptide resulting from the deacylation was critical for chemical structure determination by NMR studies, which also involved addition of calcium ions to stabilize a conformer.

Chondroitin sulfate proteoglycans in the rat thalamus: expression during postnatal development and correlation with calcium-binding proteins in adults.

Postnatal expression of chondroitin sulfate proteoglycans was studied in the rat thalamus by immunocytochemistry and Western immunoblotting techniques with monoclonal antibodies that recognize carbohydrate epitopes (clones CS-56, 1-B-5, 2-B-6). The complex of the results shows that these antibodies recognize mostly nonoverlapping molecules whose expression is regulated during postnatal development. Chondroitin sulfate proteoglycans, recognized by antibody CS-56, and hyaluronan, identified by antibody 1-B-5 after hyaluronidase digestion, are abundant in the neuropil of most thalamic nuclei at the perinatal stage and progressively decrease during the second week of life, attaining levels barely detectable by immunocytochemistry at the end of the third week. In adult thalamus, chondroitin sulfate proteoglycans of high molecular mass, bearing glycosaminoglycans unsulfated in the linking region, and recognized by antibody 1-B-5 are confined to perineuronal nets around neurons chiefly localized in thalamic reticular nucleus. The immunoreactvity for antibody 2-B-6, specific for chondroitin-4-sulfate, is low at the perinatal stage and is not detectable in adult thalamus. Double-immunolabeling has shown that, along the rostrocaudal extension of reticular nucleus, the most developed perineuronal nets are associated with a subset of neurons expressing calretinin, and not with parvalbumin-positive neurons, which represent the largest neuronal population of the nucleus. The distribution of perineuronal nets supports the presence, in thalamic reticular nucleus, of neuronal subpopulations with different morphological and physiological features.

Parvalbumin and GABA in the developing somatosensory thalamus of the rat: an immunocytochemical ultrastructural correlation.

The calcium binding protein parvalbumin (PV) is widely distributed in the mammalian nervous system and its relationship with GABAergic neurons differs within thalamic nuclei and animal species. In the rat somatosensory thalamus PV immunoreactive (ir) neurons were found only in the GABAergic reticular thalamic nucleus (RT), while a dense PVir neuropil is present in the ventrobasal complex (VB). In this study the distribution and relationship of PV and GABA were investigated in RT and VB during postnatal development at electron microscopic level. The pre-embedding immunoperoxidase detection of PV was combined with the post-embedding immunogold localization of GABA. In RT, at all developmental ages, neuronal cell bodies, dendrites and rare axonal terminals were both PVir and GABAir. In VB during the first postnatal week several small vesicle-containing profiles were double-labelled and some of them were identifiable as synaptic terminals. From postnatal day 7 (P7) to P9 the medial part of VB was more intensely PVir than the lateral one and some differences in the sequence of maturation of PVir terminals were noted between these two VB subdivisions. Single-labelled PVir profiles were first observed at P8, whereas single-labelled PVir terminals appeared at P12 and at P15 they became more frequent and larger, showing the typical morphology of ascending afferents described in adult VB. These results demonstrate the late expression of PV and acquisition of adult morphology in ascending terminals of rat VB during postnatal development in comparison with the innervation arising from the GABAergic RT.

Organization of radial and non-radial glia in the developing rat thalamus.

The organization of glia and its relationship with migrating neurons were studied in the rat developing thalamus with immunocytochemistry by using light, confocal, and electron microscopy. Carbocyanine labeling in cultured slice of the embryonic diencephalon was also used. At embryonic day (E) 14, vimentin immunoreactivity was observed in radial fascicles spanning the neuroepithelium and extending from the ventricular zone to the lateral surface of the diencephalic vesicle. Vimentin-immunopositive fibers orthogonal to the radial ones were also detected at subsequent developmental stages. At E16, radial and non-radial processes were clearly associated with migrating neurons identified by the neuronal markers calretinin and gamma-aminobutyric acid. Non-radial glial fibers were no longer evident by E19. Radial fibers were gradually replaced by immature astrocytes at the end of embryonic development. In the perinatal period, vimentin immunoreactivity labeled immature astrocytes and then gradually decreased; vimentin-immunopositive cells were only found in the internal capsule by the second postnatal week. Glial fibrillary acidic protein immunoreactivity appeared at birth in astrocytes of the internal capsule, but was not evident in most of the adult thalamic nuclei. Confocal and immunoelectron microscopy allowed direct examination of the relationships between neurons and glial processes in the embryonic thalamus, showing the coupling of neuronal membranes with both radial and non-radial glia during migration. Peculiar ultrastructural features of radial glia processes were observed. The occurrence of non-radial migration was confirmed by carbocyanine-labeled neuroblasts in E15 cultured slices. The data provide evidence that migrating thalamic cells follow both radial and non-radial glial pathways toward their destination.

Atrial septal aneurysm in a patient with pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a rare heritable disorder of the connective tissue characterized by marked clinical heterogeneity. Common cardiovascular complications of PXE include renovascular hypertension, premature coronary artery disease and calcification of peripheral arteries frequently leading to claudicatio intermittens; fibrous thickening of the endocardium and atrioventricular valves, leading to restrictive cardiomyopathy and/or mitral valve prolapse have been also described. We herein report on a PXE patient who developed an atrial septal aneurysm as a previously undescribed cardiologic manifestation of her disease.

Plasma and urinary endothelin-1 titers and plasma von Willebrand activity in Pseudoxanthoma elasticum.

We found high endothelin-1 and von Willebrand factor plasma titers not only in two individuals (daughter and father) affected with Pseudoxanthoma elasticum but also in a young unaffected relative. These findings raise the possibility that these molecules could be the first biochemical fingerprints of this, still not clinically evident, rare inherited disorder of elastic tissue.

Immunocytochemical and ultrastructural study of the rat perireticular thalamic nucleus during postnatal development.

The perireticular thalamic nucleus (PRT) consists of scattered neurons that are located in the internal capsule adjacent to the gamma aminobutyric acid (GABA)-immunoreactive (ir) reticular thalamic nucleus (RT) and whose number decreases during development. The common feature of PRT neurons in different species is the immunoreactivity for the calcium binding protein parvalbumin (PV), which is also expressed by RT cells. In this study, we analyzed, at the light and electron microscopic level, the distribution and morphology of PV-ir neurons and their relationship with GABA in adult and developing rats. We found that the rostrocaudal distribution and the morphology of PV-ir neurons of the PRT were different at each stage of postnatal development examined. The adult configuration of the PV-ir population in the PRT was achieved at postnatal day 21. With electron microscopy, the developing PRT was observed to contain PV-ir neuronal cell bodies and dendrites contacted by several PV-negative synaptic terminals, some of which were GABA-ir, whereas the adult PRT contained also large PV-ir boutons, generally GABA-ir. Very few GABA-ir neurons were found in the PRT region and only during the first postnatal week, thus indicating that the PV-ir neurons of PRT represent a distinct population from those of RT. Our results demonstrate a morphological, neurochemical, and ultrastructural complexity of the PRT not only during development, but also in adulthood. These findings provide new data supporting the suggested roles of the PRT during postnatal development, and may indicate that in adult life it can play other so far unknown functions.

Postnatal development of GABA-immunoreactive terminals in the reticular and ventrobasal nuclei of the rat thalamus: a light and electron microscopic study.

The postnatal development of inhibitory GABAergic circuits in the thalamic reticular and ventrobasal nuclei was studied in rats ranging from the day of birth to the end of the third postnatal week by means of a postembedding immunogold staining procedure to visualize GABA. In the reticular nucleus, GABA labeling was present from birth in cell bodies, dendrites, growth cones and a few synaptic terminals, whereas in the ventrobasal nucleus it was exclusively in axonal processes identifiable as growth cones, vesicle-rich profiles and synaptic terminals. In both nuclei, GABA-labeled synaptic terminals were, however, very scarce and immature in neonatal animals and they became numerous and morphologically mature only after the end of the second postnatal week. These findings suggest that inhibitory synaptic responses in the somatosensory thalamus are not yet fully mature throughout the first two postnatal weeks and support the hypothesis that GABA may initially play trophic roles. The relatively late maturation of the thalamic GABAergic system may have important functional consequences, as the reticulothalamic circuits are responsible for the generation of spindle wave oscillations whose cellular mechanisms are also involved in the generation of spike-and-wave (absence) seizures in humans and in animal models.

Ultrastructural characterization of the postnatal development of the thalamic ventrobasal and reticular nuclei in the rat.

Electron microscopy has been employed to analyze the normal maturational sequence that characterizes the postnatal development of synaptic circuits in the ventrobasal (VB) and reticular (Rt) thalamic nuclei of rats at different ages (from birth to the end of the third postnatal week). Throughout the first postnatal week, similar signs of immaturity are observed in both nuclei, mainly consisting in scarcity of cytoplasmic organelles, presence of wide extracellular spaces, and absence of myelinated fibers. Several synaptic terminals are however present from birth, thus indicating that some of the afferents have already reached and contacted their thalamic target during embryonic life. Most of the terminals are small and contain only a few round, clear vesicles, and therefore their cytological features do not allow the identification of their origin. In particular, in both nuclei, terminals with flat vesicles and symmetric specialization are only rarely observed, and in VB the ascending terminals are not distinguishable from terminals of other sources as they are in adults. During the second postnatal week, progressive maturational changes in VB and Rt lead to neurons having well-developed cytoplasmic organelles and to an elaborate neuropil containing myelinated fibers and synaptic terminals that are morphologically heterogeneous and resemble the adult ones. The permanence of growth cone-like profiles and of numerous somatic and dendritic protrusions, often contacted by synaptic terminals, indicates that a certain degree of reorganization is still taking place in both nuclei. By the end of the third postnatal week the synaptic organization of VB and Rt is indistinguishable from that observed in adults. This ultrastructural study shows that the appearance of the neuropil of VB and Rt and the morphological complexity of the synaptic arrangements characteristic of the adult rat are not present in neonates, but are gradually acquired during the first three postnatal weeks, and that they result from progressive modifications in circuit organization involving both pre- and postsynaptic elements.

Ultrastructural immunolocalization of muscarinic acetylcholine receptor in the dorsal thalamus of rat.

The ultrastructural distribution of muscarinic acetylcholine receptor (mAChR) in the dorsal thalamus of the adult rat was studied by means of pre-embedding immunocytochemistry using the monoclonal antibody M35. mAChR immunoreactivity (ir) was present with variable intensity in the different thalamic nuclei, but with a similar subcellular localization. Labeling was restricted to neuronal cell bodies and dendrites, where it was both in the cytoplasm and along the cytoplasmic side of the plasma membrane, in areas post-synaptic to small terminals with round clear vesicles but also in non-synaptic areas. Glial cells were unlabeled. By combining the pre-embedding immunostaining for mAChR with post-embedding immunogold labeling for GABA it was shown that GABAergic terminals made synaptic contacts with cholinoceptive structures, but no mAChR ir was present at their post-synaptic sites.

Enrichment of glutamate immunoreactivity in lemniscal terminals in the ventropostero lateral thalamic nucleus of the rat: an immunogold and WGA-HRP study.

BACKGROUND: The ventropostero lateral nucleus (VPL) is a thalamic somatosensory center receiving inputs from limbs and trunk; some of this input is via terminals of the dorsal column medial lemniscal pathway. These fibers convey non-noxious somesthesic information. METHODS: In this study the neurochemical content of lemniscal afferents in VPL of rats was investigated at the electron microscopic level by combining anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin, injected in the dorsal dorsal column nuclei, with postembedding immunogold labeling for glutamate (Glu). RESULTS: Anterograde labeling in VPL was detected only in myelinated axons and in large terminals containing round synaptic vesicles, interpreted as lemniscal afferents. Quantitative evaluation of gold particle density showed enrichment of Glu immunolabeling in the identified lemniscal terminals with respect to other neuronal profiles. Observation of serial sections immunoreacted for Glu demonstrated consistency of labeling, whereas in alternate sections immunoreacted for Glu and for the inhibitory amino acid GABA these two antigens were always present in distinct types of terminals. CONCLUSIONS: These findings are in agreement with several lines of evidence, obtained with different experimental approaches, supporting the hypothesis that Glu plays a major role in conveying sensory stimuli to the thalamus from second order neurons in the dorsal column nuclei.

Branching projections from mesopontine nuclei to the nucleus reticularis and related thalamic nuclei: a double labelling study in the rat.

Branching projections from pedunculopontine and laterodorsal tegmental nuclei to different thalamic targets were studied by means of a double retrograde tracing technique. The results show a topographic distribution of mesopontine neurons projecting to different thalamic targets. In addition, the present data demonstrate that a small percentage (< or = 5%) of mesopontine neurons projecting to the intralaminar nuclei or to the rostral pole of the reticular nucleus innervate both these areas by means of branching axons. By contrast, a large number of mesopontine neurons projecting to the sensorimotor thalamic nuclei send axon collaterals to the caudal part of the reticular nucleus. The present findings support the hypothesis of an inhomogeneity of different sectors of the thalamic reticular nucleus. Thus, this nucleus can be differentiated into two functional areas, in accordance with their connections with functionally different cortical fields and thalamic districts. The possibility that these two areas of the thalamic reticular nucleus subserve different mechanisms during sleep phenomena is discussed.

GABAA-receptor immunoreactivity in the rat dorsal thalamus: an ultrastructural investigation.

The ultrastructural localization of GABAA-receptor (GABAA-R) immunoreactivity (ir) in representative nuclei of the rat dorsal thalamus was investigated using the monoclonal antibody 62-3G1 to the beta 2 and beta 3 subunits of the GABAA-R [8]. The pattern of distribution and the subcellular localization of ir were similar in all the thalamic nuclei examined, with the exception of the reticular nucleus that was unlabeled. The reaction product was present along somatic and dendritic plasma membranes of thalamic neurons and on their intracellular membranes. No labelling was observed in glial cells. The ir was present in areas of plasma membranes related and non related to terminals containing flat vesicles, and also on invaginated plasma membranes suggesting a recycling process of the receptor complex. The distribution and mismatches between GABA neurotransmitter and its receptor localization are discussed.