Anil Bhatia - Academia.edu (original) (raw)

Papers by Anil Bhatia

Operative Brachial Plexus Surgery, 2021

The treatment of brachial plexus injuries is aimed at restoration of the brain’s control on the p... more The treatment of brachial plexus injuries is aimed at restoration of the brain’s control on the paralyzed upper limb. In the presence of avulsions of multiple roots, one has to rely on transferring functioning nerves from outside the brachial plexus. Apart from associated rib fractures, the intercostal nerves are usually preserved and available for transfer. These have been utilized in attempting restoration of a variety of functions. By consensus, restoration of elbow flexion has been the priority in most cases, and the transfer of intercostal nerves has been found most useful for this purpose. Direct repairs to the target nerves have been shown to provide vastly superior results. The technique of harvesting the intercostal nerves is demanding but relatively risk-free. The long course of each nerve along the corresponding rib allows us to achieve direct approximation to the target nerve(s) in the axilla without any tension. Hence, intercostal nerve transfers are currently preferred for restoration of elbow flexion in the treatment of total or near-total brachial plexus injuries.

Annales de chirurgie de la main et du membre supérieur, 1997

RI~SUMI~ : The different types of distal insertions of the tendons of the abductor pollicis longu... more RI~SUMI~ : The different types of distal insertions of the tendons of the abductor pollicis longus muscle (APL) were studied in 104 cadaveric hands, and the appearence of the rhizarthrosis in the level of the basal joint of the thumb, as well, in a try to detect possible anatomical relationships. From the anatomical point of view, it was evident that the insertions of the APL muscle are usually multiple (95 %), that the insertion to the base of the first metacarpal is constantly present, accompanied in 70 % of the cases with an insertion to the trapezium. Finally, the accessory tendon to the thenar eminence was proved to be extremely frequent (42 %). Rhizarthrosis has been found in 97 % of the dissections. The lateral compartment of the joint surface appeared to be the most frequently affected with arthritis (71%) and probably the starting point of the lesion. But no correlation has been recorded between severe arthritis and any type of distal insertion of abductor pollicis longus muscle. Early tenotomy of some tendons, in order to prevent arthritis of the first CMC joint, cannot be recommended from this study.

The journal of hand surgery, Jun 1, 1995

Vohwinkel syndrome or hereditary mutilating keratodermatitis is a rare condition producing palmop... more Vohwinkel syndrome or hereditary mutilating keratodermatitis is a rare condition producing palmoplantar hyperkeratosis and constricting rings of the fingers and toes which can progress to compromise neurovascular function and mobility. Medical treatment with oral retinol derivatives is recommended when its use is not contra-indicated. This paper describes surgical correction of the constricting rings on both hands in a 33-year-old woman affected by this condition.

Annales de chirurgie de la main et du membre supérieur, 1997

Rt~SUMt~: Les auteurs rapportent 18 cas de transferts de quelques fascicules du nerf ulnaire sur ... more Rt~SUMt~: Les auteurs rapportent 18 cas de transferts de quelques fascicules du nerf ulnaire sur le nerf du muscle biceps, r6alis6s entre 1990 et 1997. Les patients 6taient fig6s de 17 fi 41 ans, et pr6sentaient une paralysie C5 C6 dans 8 cas et C5 C6 C7 dans 10 cas. Uintervention a 6t6 tent6e entre 4 mois et 6 ans (m = 17 mois) apr6s l'accident initial. Dans les paralysies C5 C6 revues (n = 8), 7 patients ont r6cup6r6 une flexion du coude, un seul ayant n6cessit6 un transfert d'appoint selon Steindler. Dans les paralysies C5 C6 C7 revues (n = 9), 4 patients ont r6cup6r6 une flexion du coude par la seule chirurgie nerveuse, tandis que 4 ne l'ont obtenue qu'apr6s un transfert de Steindler compl6mentaire faisant passer la force de flexion du grade 2 au grade 3. Parmi ces 4 patients, deux avaient 6t6 op6r6s tr6s tardivement (27 et 75 mois). Enfin, 1 seul patient, fig6 de 40 ans et op~r6 28 mois apr6s l'accident a eu 1 6chec complet. Au total, le transfert nerveux ~< ulnaire biceps >> apparait au mieux indiqu6 dans les avulsions C5 C6 du plexus brachial, et dans les mois suivant l'accident initial. Une flexion contre pesanteur est alors r6guli6rement obtenue en moins de 6 mois, sans s6quelles objectives ou subjectives fi la main.

EMC - Techniche Chirurgiche - Chirurgica Ortopedica, 2005

Riassunto Il chirurgo, ortopedico o plastico, deve distinguere tra i vari tipi di piaghe da decub... more Riassunto Il chirurgo, ortopedico o plastico, deve distinguere tra i vari tipi di piaghe da decubito. Le piaghe da compressione nei pazienti debilitati affetti da malattie con prognosi grave o da cachessia devono essere escluse dai tratta-menti chirurgici. Le piaghe vanno trattate chirurgicamente soltanto nei pazienti in buone condizioni generali o nei pazienti affetti da paralisi persistente. Le piaghe da decubito corrispondono a zone di necrosi avascolare dovuta a eccessiva compressione. La lesione cutanea e soltanto una parte di un’area ischemica in genere molto estesa che comprende i tessuti sottocutanei e muscolari, con infezione ossea profonda ecc. La prima e piu importante fase della procedura chirurgica consiste in un esteso sbrigliamento, con escissione sistematica di ogni tessuto ischemia o infetto. Questa e la parte piu difficile dell’intervento e richiede un chirurgo esperto. La seconda fase consiste nel riempire la lesione con tessuto solido, spesso e scorrevole per prevenire una recidiva dell’ulcerazione. Le piaghe trocanteriche vengono trattate di routine con un lembo di tensore della fascia lata e le piaghe sacrali con il lembo gluteo muscolocutaneo di rotazione, mentre quelle ischiatiche in genere possono essere chiuse di prima intenzione, meno frequentemente con un lembo proveniente dalla faccia posteriore della coscia.

The journal of hand surgery, Jun 1, 1995

A salvage technique for the treatment of substance loss of the extensor apparatus with some speci... more A salvage technique for the treatment of substance loss of the extensor apparatus with some special features is presented. It uses the extensor indicis muscle prolonged with a tendon graft. The tendon is directly attached to the middle phalanx. After surgery, the wrist is immobilized in extension, allowing immediate active mobilization of the PIP joint. The results in five patients are satisfactory.

Surgical and Radiologic Anatomy, Nov 1, 1998

A morphometric study has shown that 10% of the fibers of the ulnar nerve should suffice to reinne... more A morphometric study has shown that 10% of the fibers of the ulnar nerve should suffice to reinnervate the biceps muscle in brachial plexus palsies. The aim of this study was to evaluate, by a morphometric study using computerized microanalysis, the cross-sectional surface areas of the different collateral and terminal branches of the ulnar nerve. This was expressed in terms of percentage of the cross-sectional surface area of the main trunk of the ulnar nerve. The study revealed that the branch to the flexor digitorum profundus bellies to the ring and little fingers formed 9.5% of the cross-sectional area of the ulnar nerve. Thus use of these fascicles destined for the flexor digitorum profundus, identified by intra-operative nerve stimulation, at the level of the arm would be sufficient for neurotisation of the nerve to the biceps. This has been confirmed by the initial clinical results in patients operated upon using this technique.

Nature Communications, 2022

The RAP (RNA-binding domain abundant in Apicomplexans) protein family has been identified in vari... more The RAP (RNA-binding domain abundant in Apicomplexans) protein family has been identified in various organisms. Despite expansion of this protein family in apicomplexan parasites, their main biological functions remain unknown. In this study, we use inducible knockdown studies in the human malaria parasite, Plasmodium falciparum, to show that two RAP proteins, PF3D7_0105200 (PfRAP01) and PF3D7_1470600 (PfRAP21), are essential for parasite survival and localize to the mitochondrion. Using transcriptomics, metabolomics, and proteomics profiling experiments, we further demonstrate that these RAP proteins are involved in mitochondrial RNA metabolism. Using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (eCLIP-seq), we validate that PfRAP01 and PfRAP21 are true RNA-binding proteins and interact specifically with mitochondrial rRNAs. Finally, mitochondrial enrichment experiments followed by deep sequencing of small RNAs demonstrate that PfRAP21 controls mit...

Current Research in Toxicology, 2021

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that, upon activation ... more Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that, upon activation by ligands, heterodimerizes with retinoid X receptor (RXR), binds to PPAR response elements (PPREs), and activates transcription of downstream genes. As PPARγ plays a central role in adipogenesis, fatty acid storage, and glucose metabolism, PPARγ-specific pharmaceuticals (e.g., thiazolidinediones) have been developed to treat Type II diabetes and obesity within human populations. However, to our knowledge, no prior studies have concurrently assessed the effects of PPARγ ligand exposure on genome-wide PPARγ binding as well as effects on the transcriptome and lipidome within human cells at biologically active, non-cytotoxic concentrations. In addition to quantifying concentration-dependent effects of ciglitazone (a reference PPARγ agonist) and GW 9662 (a reference PPARγ antagonist) on human hepatocarcinoma (HepG2) cell viability, PPARγ abundance in situ, and neutral lipids, HepG2 cells were exposed to either vehicle (0.1% DMSO), ciglitazone, or GW 9662 for up to 24 h, and then harvested for 1) chromatin immunoprecipitation-sequencing (ChIP-seq) to identify PPARγ-bound regions across the entire genome, 2) mRNA-sequencing (mRNA-seq) to identify potential impacts on the transcriptome, and 3) lipidomics to identify potential alterations in lipid profiles. Following exposure to ciglitazone and GW 9662, we found that PPARγ levels were not significantly different after 2-8 h of exposure. While ciglitazone and GW 9662 resulted in a concentration-dependent increase in neutral lipids, the magnitude and localization of PPARγ-bound regions across the genome (as identified by ChIP-seq) did not vary by treatment. However, mRNA-seq and lipidomics revealed that exposure of HepG2 cells to ciglitazone and GW 9662 resulted in significant, treatment-specific effects on the transcriptome and lipidome. Overall, our findings suggest that exposure of human cells to PPARγ ligands at biologically active, noncytotoxic concentrations results in toxicity that may be driven by a combination of both PPARγ-dependent and PPARγ-independent mechanisms.

Annales de Chirurgie de la Main et du Membre Supérieur, 1996

The STT joint was examined in 73 fresh cadaveric specimens (25 male and 48 female with an average... more The STT joint was examined in 73 fresh cadaveric specimens (25 male and 48 female with an average age of 84 years) with a view to study the incidence and characteristics of degenerative changes in this joint. The articular degeneration was graded from 0 to 3 according to increasing loss of cartilage and the location of the changes was noted. At the same time, the presence and extent of concomitant trapezio-metacarpal arthritis was noted. 61 of the 73 hands (83.3 %) were found to present STT arthritis. Degeneration of the trapezoid articular surface was :-more frequent: 53 hands (72.6%) as compared to 48 (65.7%),-of greater severity: 40 cases (55 %) of grades 2/3 as compared to 25 (34 %), than that of the trapezium. Concomitant or isolated arthritis in the trapezometacarpal joint (90.4%) was present in 66 of the 73 hands (79 %) examined with grade 3 changes in 13 cases. The apparent predominance of degeneration in the scapho trapezoidal articulation could, perhaps, lead us to assume that this might be the site of origin of STT arthritis. It could also explain the persistence of symptoms following prosthetic replacement of the trapezium.

Plastic and Reconstructive Surgery, 2001

Operative Brachial Plexus Surgery, 2021

A deltoid and teres minor muscle palsy can occur after an isolated axillary nerve injury or a pos... more A deltoid and teres minor muscle palsy can occur after an isolated axillary nerve injury or a posterior cord or upper brachial plexus injury. Several considerations should be taken into account when planning an axillary nerve reconstruction. A surgical exploration at the site of injury should be performed. Nerve grafting is our first reconstructive option with nerve transfer as a secondary alternative. The history, surgical anatomy, and indication of the anterior axillary approach as well as the triceps nerve branch to the axillary nerve transfer will be reviewed.

Textbook of Orthopedics and Trauma (4 Volumes), 2016

Operative Brachial Plexus Surgery, 2021

The role of early microsurgical reconstruction in total birth palsies cannot be disputed. Surgery... more The role of early microsurgical reconstruction in total birth palsies cannot be disputed. Surgery inevitably involves comprehensive exploration of the injured area and re-establishment of the brain’s control of the paralysed upper limb by bridging viable proximal stumps of the broken roots to the suitable distal targets. The extent of functional recovery depends largely on the strategy employed during the nerve operation. With increasing confidence in the quality of motor and sensory outcomes and the consistent results obtained with extra-plexal nerve transfers, we can, now, aim at restoring functions of the shoulder, elbow and the hand with the main objective being to maximize hand function. Since the upper limb continues to evolve over 6–8 years, diligent and relentless physical therapy is necessary to help incorporate the regained motor abilities in bimanual activities. The children have to be observed closely to prevent appearance and progression of deformities at the shoulder and elbow. Secondary operations are necessary to augment the range of shoulder motion, to correct forearm deformities and to correct residual deficits of wrist and finger extension. This extended and aggressive approach offers us the possibility of restoring full upper limb function in total palsies instead of merely creating a helping hand.

Indian journal of plastic surgery : official publication of the Association of Plastic Surgeons of India

Indian Journal of Orthopaedics, 2011

Introduction: Brachial plexus injury leading to flail upper limb is one of the most disabling inj... more Introduction: Brachial plexus injury leading to flail upper limb is one of the most disabling injuries. Neglect of the injury and delay in surgeries may preclude reinnervation of the paralysed muscles. Currently for such injuries nerve transfers are the preferred procedures. We here present a series of 93 cases of global brachial plexus palsy treated with nerve transfers. Materials and Methods: Ninety-three cases of global palsies out of 384 cases of brachial plexus injury operated by the senior surgeon (AB) were selected. Age varied from 4 to 51 years with 63 patients in 20 to 40 age group and all patients having a minimum follow up of at least 1 year post surgery ranging up to 130 months. The delay before surgery ranged from 15 days to 16 months (mean 3.2 months). The aim of the surgery was to restore the elbow flexion, shoulder abduction, triceps function and wrist and finger flexion in that order of priority. The major nerve transfers used were spinal accessory to suprascapular nerve, intercostal to musculocutaneous nerve and pectoral nerves, contralateral C7 to median and radial nerves. Nerve stumps were used whenever available (30 patients). Results: Recovery of ≥ grade 3 power was noted in biceps in 73% (68/93) of patients, shoulder abduction in 89% (43/49), pectoralis major in 100% (8/8). Recovery of grade 2 triceps power was seen in 80% (12/16) patients with nerve transfer to radial nerve. Derotation osteotomies of humerus (n=13) and wrist fusion (n=14) were the most common secondary procedures performed to facilitate alignment and movements of the affected limb. Better results were noted in 59 cases where direct nerve transfers were done (without nerve graft). Conclusion: Acceptable function (restoration of biceps power ≥3) can be obtained in more than two thirds (73%) of these global brachial plexus injuries by using the principles of early exploration and nerve transfer with rehabilitation.

The Journal of Hand Surgery

Indian Journal of Plastic Surgery

Introduction Posttraumatic brachial plexus injuries are devastating, as the brain and spinal cord... more Introduction Posttraumatic brachial plexus injuries are devastating, as the brain and spinal cord are disconnected from the upper limb. Restoration of elbow flexion has been widely recognized as the primary objective of nerve reconstruction. In the absence of utilizable (ruptured) root stumps in the neck, one has recourse only to nerve transfers. The direct transfer of intercostal nerves to the musculocutaneous nerve is one of the techniques that has been commonly employed over the past four decades. However, the outcomes of this procedure cited in the literature have varied considerably. The patient’s age and the delay from the accident to surgery have been known to affect the results of nerve reconstruction operations. The authors present a study of the effect of these parameters on intercostal nerve transfers. Methods The data of 232 patients with total and near-total brachial plexus injuries treated by the senior author between April 1995 and December 2015 was examined. Intercos...

Indian Journal of Plastic Surgery

Introduction There is consensus on the need for early microsurgical reconstruction in birth palsi... more Introduction There is consensus on the need for early microsurgical reconstruction in birth palsies involving three or more roots, that is, extensive partial palsies and total palsies. The fundamental principles of these operations are complete exploration and judicious use of the ruptured stumps by nerve grafting to suitable distal targets. The frequent observation of root avulsions in such cases makes it imperative to look for extraplexual nerve donors for some functions. Intercostal nerves are readily available in such patients. Materials and Methods This is a study of 50 patients of extensive partial and total birth palsies operated upon by the senior author between 1995 and 2010. These included 33 patients with total palsies, 16 patients with near total palsies, and one patient with C56 deficit (operated upon more than 20 years ago). These children were all operated upon between 3 and 6 months of age, except for two patients in whom surgery was delayed till a year due to the ph...

Operative Brachial Plexus Surgery, 2021

The treatment of brachial plexus injuries is aimed at restoration of the brain’s control on the p... more The treatment of brachial plexus injuries is aimed at restoration of the brain’s control on the paralyzed upper limb. In the presence of avulsions of multiple roots, one has to rely on transferring functioning nerves from outside the brachial plexus. Apart from associated rib fractures, the intercostal nerves are usually preserved and available for transfer. These have been utilized in attempting restoration of a variety of functions. By consensus, restoration of elbow flexion has been the priority in most cases, and the transfer of intercostal nerves has been found most useful for this purpose. Direct repairs to the target nerves have been shown to provide vastly superior results. The technique of harvesting the intercostal nerves is demanding but relatively risk-free. The long course of each nerve along the corresponding rib allows us to achieve direct approximation to the target nerve(s) in the axilla without any tension. Hence, intercostal nerve transfers are currently preferred for restoration of elbow flexion in the treatment of total or near-total brachial plexus injuries.

Annales de chirurgie de la main et du membre supérieur, 1997

RI~SUMI~ : The different types of distal insertions of the tendons of the abductor pollicis longu... more RI~SUMI~ : The different types of distal insertions of the tendons of the abductor pollicis longus muscle (APL) were studied in 104 cadaveric hands, and the appearence of the rhizarthrosis in the level of the basal joint of the thumb, as well, in a try to detect possible anatomical relationships. From the anatomical point of view, it was evident that the insertions of the APL muscle are usually multiple (95 %), that the insertion to the base of the first metacarpal is constantly present, accompanied in 70 % of the cases with an insertion to the trapezium. Finally, the accessory tendon to the thenar eminence was proved to be extremely frequent (42 %). Rhizarthrosis has been found in 97 % of the dissections. The lateral compartment of the joint surface appeared to be the most frequently affected with arthritis (71%) and probably the starting point of the lesion. But no correlation has been recorded between severe arthritis and any type of distal insertion of abductor pollicis longus muscle. Early tenotomy of some tendons, in order to prevent arthritis of the first CMC joint, cannot be recommended from this study.

The journal of hand surgery, Jun 1, 1995

Vohwinkel syndrome or hereditary mutilating keratodermatitis is a rare condition producing palmop... more Vohwinkel syndrome or hereditary mutilating keratodermatitis is a rare condition producing palmoplantar hyperkeratosis and constricting rings of the fingers and toes which can progress to compromise neurovascular function and mobility. Medical treatment with oral retinol derivatives is recommended when its use is not contra-indicated. This paper describes surgical correction of the constricting rings on both hands in a 33-year-old woman affected by this condition.

Annales de chirurgie de la main et du membre supérieur, 1997

Rt~SUMt~: Les auteurs rapportent 18 cas de transferts de quelques fascicules du nerf ulnaire sur ... more Rt~SUMt~: Les auteurs rapportent 18 cas de transferts de quelques fascicules du nerf ulnaire sur le nerf du muscle biceps, r6alis6s entre 1990 et 1997. Les patients 6taient fig6s de 17 fi 41 ans, et pr6sentaient une paralysie C5 C6 dans 8 cas et C5 C6 C7 dans 10 cas. Uintervention a 6t6 tent6e entre 4 mois et 6 ans (m = 17 mois) apr6s l'accident initial. Dans les paralysies C5 C6 revues (n = 8), 7 patients ont r6cup6r6 une flexion du coude, un seul ayant n6cessit6 un transfert d'appoint selon Steindler. Dans les paralysies C5 C6 C7 revues (n = 9), 4 patients ont r6cup6r6 une flexion du coude par la seule chirurgie nerveuse, tandis que 4 ne l'ont obtenue qu'apr6s un transfert de Steindler compl6mentaire faisant passer la force de flexion du grade 2 au grade 3. Parmi ces 4 patients, deux avaient 6t6 op6r6s tr6s tardivement (27 et 75 mois). Enfin, 1 seul patient, fig6 de 40 ans et op~r6 28 mois apr6s l'accident a eu 1 6chec complet. Au total, le transfert nerveux ~< ulnaire biceps >> apparait au mieux indiqu6 dans les avulsions C5 C6 du plexus brachial, et dans les mois suivant l'accident initial. Une flexion contre pesanteur est alors r6guli6rement obtenue en moins de 6 mois, sans s6quelles objectives ou subjectives fi la main.

EMC - Techniche Chirurgiche - Chirurgica Ortopedica, 2005

Riassunto Il chirurgo, ortopedico o plastico, deve distinguere tra i vari tipi di piaghe da decub... more Riassunto Il chirurgo, ortopedico o plastico, deve distinguere tra i vari tipi di piaghe da decubito. Le piaghe da compressione nei pazienti debilitati affetti da malattie con prognosi grave o da cachessia devono essere escluse dai tratta-menti chirurgici. Le piaghe vanno trattate chirurgicamente soltanto nei pazienti in buone condizioni generali o nei pazienti affetti da paralisi persistente. Le piaghe da decubito corrispondono a zone di necrosi avascolare dovuta a eccessiva compressione. La lesione cutanea e soltanto una parte di un’area ischemica in genere molto estesa che comprende i tessuti sottocutanei e muscolari, con infezione ossea profonda ecc. La prima e piu importante fase della procedura chirurgica consiste in un esteso sbrigliamento, con escissione sistematica di ogni tessuto ischemia o infetto. Questa e la parte piu difficile dell’intervento e richiede un chirurgo esperto. La seconda fase consiste nel riempire la lesione con tessuto solido, spesso e scorrevole per prevenire una recidiva dell’ulcerazione. Le piaghe trocanteriche vengono trattate di routine con un lembo di tensore della fascia lata e le piaghe sacrali con il lembo gluteo muscolocutaneo di rotazione, mentre quelle ischiatiche in genere possono essere chiuse di prima intenzione, meno frequentemente con un lembo proveniente dalla faccia posteriore della coscia.

The journal of hand surgery, Jun 1, 1995

A salvage technique for the treatment of substance loss of the extensor apparatus with some speci... more A salvage technique for the treatment of substance loss of the extensor apparatus with some special features is presented. It uses the extensor indicis muscle prolonged with a tendon graft. The tendon is directly attached to the middle phalanx. After surgery, the wrist is immobilized in extension, allowing immediate active mobilization of the PIP joint. The results in five patients are satisfactory.

Surgical and Radiologic Anatomy, Nov 1, 1998

A morphometric study has shown that 10% of the fibers of the ulnar nerve should suffice to reinne... more A morphometric study has shown that 10% of the fibers of the ulnar nerve should suffice to reinnervate the biceps muscle in brachial plexus palsies. The aim of this study was to evaluate, by a morphometric study using computerized microanalysis, the cross-sectional surface areas of the different collateral and terminal branches of the ulnar nerve. This was expressed in terms of percentage of the cross-sectional surface area of the main trunk of the ulnar nerve. The study revealed that the branch to the flexor digitorum profundus bellies to the ring and little fingers formed 9.5% of the cross-sectional area of the ulnar nerve. Thus use of these fascicles destined for the flexor digitorum profundus, identified by intra-operative nerve stimulation, at the level of the arm would be sufficient for neurotisation of the nerve to the biceps. This has been confirmed by the initial clinical results in patients operated upon using this technique.

Nature Communications, 2022

The RAP (RNA-binding domain abundant in Apicomplexans) protein family has been identified in vari... more The RAP (RNA-binding domain abundant in Apicomplexans) protein family has been identified in various organisms. Despite expansion of this protein family in apicomplexan parasites, their main biological functions remain unknown. In this study, we use inducible knockdown studies in the human malaria parasite, Plasmodium falciparum, to show that two RAP proteins, PF3D7_0105200 (PfRAP01) and PF3D7_1470600 (PfRAP21), are essential for parasite survival and localize to the mitochondrion. Using transcriptomics, metabolomics, and proteomics profiling experiments, we further demonstrate that these RAP proteins are involved in mitochondrial RNA metabolism. Using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (eCLIP-seq), we validate that PfRAP01 and PfRAP21 are true RNA-binding proteins and interact specifically with mitochondrial rRNAs. Finally, mitochondrial enrichment experiments followed by deep sequencing of small RNAs demonstrate that PfRAP21 controls mit...

Current Research in Toxicology, 2021

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that, upon activation ... more Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that, upon activation by ligands, heterodimerizes with retinoid X receptor (RXR), binds to PPAR response elements (PPREs), and activates transcription of downstream genes. As PPARγ plays a central role in adipogenesis, fatty acid storage, and glucose metabolism, PPARγ-specific pharmaceuticals (e.g., thiazolidinediones) have been developed to treat Type II diabetes and obesity within human populations. However, to our knowledge, no prior studies have concurrently assessed the effects of PPARγ ligand exposure on genome-wide PPARγ binding as well as effects on the transcriptome and lipidome within human cells at biologically active, non-cytotoxic concentrations. In addition to quantifying concentration-dependent effects of ciglitazone (a reference PPARγ agonist) and GW 9662 (a reference PPARγ antagonist) on human hepatocarcinoma (HepG2) cell viability, PPARγ abundance in situ, and neutral lipids, HepG2 cells were exposed to either vehicle (0.1% DMSO), ciglitazone, or GW 9662 for up to 24 h, and then harvested for 1) chromatin immunoprecipitation-sequencing (ChIP-seq) to identify PPARγ-bound regions across the entire genome, 2) mRNA-sequencing (mRNA-seq) to identify potential impacts on the transcriptome, and 3) lipidomics to identify potential alterations in lipid profiles. Following exposure to ciglitazone and GW 9662, we found that PPARγ levels were not significantly different after 2-8 h of exposure. While ciglitazone and GW 9662 resulted in a concentration-dependent increase in neutral lipids, the magnitude and localization of PPARγ-bound regions across the genome (as identified by ChIP-seq) did not vary by treatment. However, mRNA-seq and lipidomics revealed that exposure of HepG2 cells to ciglitazone and GW 9662 resulted in significant, treatment-specific effects on the transcriptome and lipidome. Overall, our findings suggest that exposure of human cells to PPARγ ligands at biologically active, noncytotoxic concentrations results in toxicity that may be driven by a combination of both PPARγ-dependent and PPARγ-independent mechanisms.

Annales de Chirurgie de la Main et du Membre Supérieur, 1996

The STT joint was examined in 73 fresh cadaveric specimens (25 male and 48 female with an average... more The STT joint was examined in 73 fresh cadaveric specimens (25 male and 48 female with an average age of 84 years) with a view to study the incidence and characteristics of degenerative changes in this joint. The articular degeneration was graded from 0 to 3 according to increasing loss of cartilage and the location of the changes was noted. At the same time, the presence and extent of concomitant trapezio-metacarpal arthritis was noted. 61 of the 73 hands (83.3 %) were found to present STT arthritis. Degeneration of the trapezoid articular surface was :-more frequent: 53 hands (72.6%) as compared to 48 (65.7%),-of greater severity: 40 cases (55 %) of grades 2/3 as compared to 25 (34 %), than that of the trapezium. Concomitant or isolated arthritis in the trapezometacarpal joint (90.4%) was present in 66 of the 73 hands (79 %) examined with grade 3 changes in 13 cases. The apparent predominance of degeneration in the scapho trapezoidal articulation could, perhaps, lead us to assume that this might be the site of origin of STT arthritis. It could also explain the persistence of symptoms following prosthetic replacement of the trapezium.

Plastic and Reconstructive Surgery, 2001

Operative Brachial Plexus Surgery, 2021

A deltoid and teres minor muscle palsy can occur after an isolated axillary nerve injury or a pos... more A deltoid and teres minor muscle palsy can occur after an isolated axillary nerve injury or a posterior cord or upper brachial plexus injury. Several considerations should be taken into account when planning an axillary nerve reconstruction. A surgical exploration at the site of injury should be performed. Nerve grafting is our first reconstructive option with nerve transfer as a secondary alternative. The history, surgical anatomy, and indication of the anterior axillary approach as well as the triceps nerve branch to the axillary nerve transfer will be reviewed.

Textbook of Orthopedics and Trauma (4 Volumes), 2016

Operative Brachial Plexus Surgery, 2021

The role of early microsurgical reconstruction in total birth palsies cannot be disputed. Surgery... more The role of early microsurgical reconstruction in total birth palsies cannot be disputed. Surgery inevitably involves comprehensive exploration of the injured area and re-establishment of the brain’s control of the paralysed upper limb by bridging viable proximal stumps of the broken roots to the suitable distal targets. The extent of functional recovery depends largely on the strategy employed during the nerve operation. With increasing confidence in the quality of motor and sensory outcomes and the consistent results obtained with extra-plexal nerve transfers, we can, now, aim at restoring functions of the shoulder, elbow and the hand with the main objective being to maximize hand function. Since the upper limb continues to evolve over 6–8 years, diligent and relentless physical therapy is necessary to help incorporate the regained motor abilities in bimanual activities. The children have to be observed closely to prevent appearance and progression of deformities at the shoulder and elbow. Secondary operations are necessary to augment the range of shoulder motion, to correct forearm deformities and to correct residual deficits of wrist and finger extension. This extended and aggressive approach offers us the possibility of restoring full upper limb function in total palsies instead of merely creating a helping hand.

Indian journal of plastic surgery : official publication of the Association of Plastic Surgeons of India

Indian Journal of Orthopaedics, 2011

Introduction: Brachial plexus injury leading to flail upper limb is one of the most disabling inj... more Introduction: Brachial plexus injury leading to flail upper limb is one of the most disabling injuries. Neglect of the injury and delay in surgeries may preclude reinnervation of the paralysed muscles. Currently for such injuries nerve transfers are the preferred procedures. We here present a series of 93 cases of global brachial plexus palsy treated with nerve transfers. Materials and Methods: Ninety-three cases of global palsies out of 384 cases of brachial plexus injury operated by the senior surgeon (AB) were selected. Age varied from 4 to 51 years with 63 patients in 20 to 40 age group and all patients having a minimum follow up of at least 1 year post surgery ranging up to 130 months. The delay before surgery ranged from 15 days to 16 months (mean 3.2 months). The aim of the surgery was to restore the elbow flexion, shoulder abduction, triceps function and wrist and finger flexion in that order of priority. The major nerve transfers used were spinal accessory to suprascapular nerve, intercostal to musculocutaneous nerve and pectoral nerves, contralateral C7 to median and radial nerves. Nerve stumps were used whenever available (30 patients). Results: Recovery of ≥ grade 3 power was noted in biceps in 73% (68/93) of patients, shoulder abduction in 89% (43/49), pectoralis major in 100% (8/8). Recovery of grade 2 triceps power was seen in 80% (12/16) patients with nerve transfer to radial nerve. Derotation osteotomies of humerus (n=13) and wrist fusion (n=14) were the most common secondary procedures performed to facilitate alignment and movements of the affected limb. Better results were noted in 59 cases where direct nerve transfers were done (without nerve graft). Conclusion: Acceptable function (restoration of biceps power ≥3) can be obtained in more than two thirds (73%) of these global brachial plexus injuries by using the principles of early exploration and nerve transfer with rehabilitation.

The Journal of Hand Surgery

Indian Journal of Plastic Surgery

Introduction Posttraumatic brachial plexus injuries are devastating, as the brain and spinal cord... more Introduction Posttraumatic brachial plexus injuries are devastating, as the brain and spinal cord are disconnected from the upper limb. Restoration of elbow flexion has been widely recognized as the primary objective of nerve reconstruction. In the absence of utilizable (ruptured) root stumps in the neck, one has recourse only to nerve transfers. The direct transfer of intercostal nerves to the musculocutaneous nerve is one of the techniques that has been commonly employed over the past four decades. However, the outcomes of this procedure cited in the literature have varied considerably. The patient’s age and the delay from the accident to surgery have been known to affect the results of nerve reconstruction operations. The authors present a study of the effect of these parameters on intercostal nerve transfers. Methods The data of 232 patients with total and near-total brachial plexus injuries treated by the senior author between April 1995 and December 2015 was examined. Intercos...

Indian Journal of Plastic Surgery

Introduction There is consensus on the need for early microsurgical reconstruction in birth palsi... more Introduction There is consensus on the need for early microsurgical reconstruction in birth palsies involving three or more roots, that is, extensive partial palsies and total palsies. The fundamental principles of these operations are complete exploration and judicious use of the ruptured stumps by nerve grafting to suitable distal targets. The frequent observation of root avulsions in such cases makes it imperative to look for extraplexual nerve donors for some functions. Intercostal nerves are readily available in such patients. Materials and Methods This is a study of 50 patients of extensive partial and total birth palsies operated upon by the senior author between 1995 and 2010. These included 33 patients with total palsies, 16 patients with near total palsies, and one patient with C56 deficit (operated upon more than 20 years ago). These children were all operated upon between 3 and 6 months of age, except for two patients in whom surgery was delayed till a year due to the ph...